physiology of CNS wk 8 - important

And we're on to the nervous system. So this week, we're starting with physiology. Now, I've reworked these lectures compared to previous years and reordered the structure. So we're going to see how we get on with the new order. The reason I've reordered it is to align it more with Ross and Wilson, our standard textbook. So if you're following Ross and Wilson, hopefully that will help you out a little bit, just that we're following that order. If we don't get through everything today, it's not the end of the world. We'll just carry on with it next week. Okay, so physiology then, we are hopefully recording, although I'm not 100% convinced whether it is or isn't We'll see what it manages. Our aims and objectives then for this week, this first week, it's all about physiology. It's all about function of the nervous system. So we're going to start by looking at the structure of the neuron, and then we'll be focusing most of today on nerve conduction, how nerves transmit messages. And they do that through two different ways. We have our electrical conduction of that message and then our chemical or synaptic conduction of the message. So we'll be spending a lot of time on that part of the lecture. We'll then finish up today by looking at the structure of nerves as a whole. So rather than just neurons, individual nerve cells, we'll be looking at the nerves themselves and the different types of nerves, sensory, motor and autonomic nervous system as well. Next week, we'll be looking at the anatomy of the central nervous system. And then in our third week, we have just one hour and in that we'll be looking at the peripheral nervous system. So physiology this week and then anatomy for the next couple of weeks. What else do I want to mention? Next week, we have on Tuesday, we've got our seminar that we had to miss before Easter because I was ill. So that's been rescheduled for next Tuesday, I think it is, it's an online session. It's an online session at the end of the day. So do try and join us for that. That will be a seminar based on the muscular skeletal system. So we'll be doing some practice questions based on that material. And then next week, you also start the practicals again. You've got our final practical for this module. It's our nervous system practical. You'll be looking at the neuromuscular junction down the microscope and the assessment, the blackboard test that goes with this practical is one that counts for marks. It's a summative assessment for this one. So remember, as usual, attendance at practicals is compulsory or you get a mark penalty in the coursework, but the assessment, it will open on the 7th of May. It closes with a hard deadline of 12 o'clock on the 16th of May. And then answers marks and feedback and things come 15 days later. There we go, right. So our standard textbooks, Ross and Wilson's Anatomy and Physiology by Wharton Grant. This is where a lot of the material comes from today. And as I said, I've aligned the lecture with that textbook in terms of the order to make it a bit easier for you. Aspenal Capello, similar textbook, but more animal based. For those doing the pathology module this semester, you might also find Port's Pathology helpful. So we've met Harvey and Hannah loads of time before. They work in a conservation centre. Hannah is a clever lady. She's noticed that all the animals need various things similar to Harvey for survival. One of those things is all about communication. So the nervous system is clearly one of our key communication systems. So we have, for communication we have transport. We've looked at that in terms of a cardiovascular system, but we now need to think about communication internally and externally for the body. Internally, we've got two main communication systems. We've got the nervous system and the endocrine system. So the nervous system enables us to have a rapid communication around and within the body. So that consists of the brain, the spinal cord, and then all the peripheral nerves. The endocrine system provides a much slower means of communication. It's slower, but potentially more precise. It's a very tightly regulated system, the endocrine system, but it is much slower than our nervous conduction. Now we don't cover the endocrine system in this module, but some of you will be learning about the endocrine system in your second and third year, okay? Externally, the nervous system is also involved in external communications. We've got our special senses at our sight, from our eyes, hearing, balance, smell, and taste. We might touch on those a little when we look at the peripheral nervous system. Verbal communication is all about speech, and then non-verbal communication is about our body posture and our movements. We'll begin with a really brief overview of the nervous system, and then we'll get stuck into that physiology. So the role of the nervous system is to detect and respond to changes both inside and outside the body to help us maintain homeostasis. So it works with the endocrine system to try and manage our homeostatic condition, our balance in our body. So this involves various functions. We've got sensory perception. We need to be able to detect what's happening both internally and externally. So a perception or an awareness of the internal and the external environment. We then have cognitive functions, so our ability to process thoughts. This includes things like memory, learning, understanding or comprehension, and speech. Motor functions are our ability to control movement. So we're sending some information from the outside in towards the central nervous system, whereas other information goes from the central nervous system out to other parts of the body, so motor control. The brain controls the movement of our muscles. And then, of course, our nervous system is involved in regulatory functions, regulating things like our emotions, our appetites, our heart rate, our breathing, our body temperature, and so on. So you can see the nervous system has a huge number of roles. It brings in information, processes it all, sends out a decision or an action to be considered, and it regulates some of our most fundamental processes of life, things like breathing and heart rates and temperature. So this is a picture that comes from Ross and Wilson. It's a fairly simplified version of the nervous system. Oh, pause on that. Where were we? We were talking about our overview of the nervous system then. So this picture comes from Ross and Wilson. You can see here, we've got the central nervous system, which consists of the brain and the spinal cord. And then in yellow, you've got the peripheral nervous system. So these are those nerves that are bringing either sensations in to the central nervous system or sending out messages for things like movement, going out from the nervous system, central nervous system. So we can break it down, the nervous system into two parts, so central and peripheral. The flow chart here kind of depicts that as well. So on the left here, we've got the sensation. So sensation comes in through the peripheral nervous system to the central nervous system. The central nervous system then sends out messages such as movement messages from the central nervous system to the peripheral nervous system and then out to parts of the body. So muscles or glands or different parts of the body. We're gonna come back to this picture later on. We'll look at the detail in it later. But for now, I just want you to have an awareness, of course, that we've got the central nervous system, brain and spinal cord and peripheral nervous system, which on the picture here you're seeing as spinal nerves. Okay, so anatomically, central nervous system is brain and spinal cord. Functionally, the central nervous system is responsible for receiving input. So it receives those incoming messages or sensations, integrating or coordinating it all and then triggering some kind of response that it will send outwards. The peripheral nervous system consists of a whole different group of nerves. We've got three groups of nerves that we'll talk about in two weeks time, so in the third week. We've got spinal nerves. We've got the cranial nerves, which supply the head and the neck. And then we've got the autonomic nerves, which you've probably heard of as the flight and fight response. So our sympathetic, flight and fight, parasympathetic is our rest and digest response. So these groups of nerves, these are all part of the peripheral nervous system. Their functions then, function of the peripheral nervous system is to transmit input, so sensation. And we'll look at the different types of sensation later. So we've got general sensation like touch, temperature and pain. We've got autonomic sensation where we're detecting or sensing things internally, such as pH, so chemo receptors, baroreceptors for pressure, osmoreceptors for osmotic pressure. And then we've got our special senses, so input from our eyes, so sight, input from our ears in terms of hearing and balance, input from smell, input from taste. So we've got all of those sensations, all of those inputs. And then also the peripheral nervous system is the outputs, which typically is motor. So our somatic or general bodily motor functions are skeletal muscles, so our ability to move our bodies. But we also have autonomic motor actions as well. So we have some muscles which are under unconscious control, things like our gut peristalsis, our heart contracting, the contraction of glands to make them release juices and things like that. So these are all under our autonomic control rather than our conscious somatic control. So that kind of overviews the nervous system. I'm sure a lot of that you're already familiar with, but I just wanted to set the scene before we dive deep into the physiology, OK? So we need to make sure we understand that basic structure of central nervous system and peripheral nervous system before we can look at it at the cellular level. So when we look at the nervous system at the cellular level, there are two main types of cells in nervous tissue. Nervous tissue consists of more than one cell type. So we've got our neurons and we've got neuroglia. So the neurons are the ones in kind of gold here and the blue cells are our glial cells. The neurons are the ones which are able to generate and transmit nervous impulses, they send messages. We have about 100 billion of them in the body. And the key thing about neurons is we can't replicate them. So they can't divide and reproduce. When they get damaged, that's it, they're kind of damaged. Neuroglia, on the other hand, these, in the picture of the blue cells in the photograph here, these provide a supportive connective tissue. So they have a whole range of roles that we'll look at in a minute. There are an awful lot more of them than neurons. We think of nervous tissue as being all about transmitting messages. But actually, the majority of the nervous tissue is not the cells that transmit the messages, but these supporting cells. So we have 10 times more glial cells than we do actual neurons. And the nice thing about glial cells is they can repair and they can regenerate or replicate. Hello! Let's just pause a second. All right, let's carry on. So, the glial cells then, glial cells super important. They provide a supportive connective tissue around those neurons. Let's take a closer look at them. So there are four main types of glial cells in the central nervous system. We're gonna look at each of them in a bit more detail in a moment. But these are astrocytes, oligodendrocytes, ependymal cells, and microglia. So we've got four different types of glial cells. So you've probably heard of neurons. I'm assuming you've heard of those. But you might not have done so much on the glial cells. Let's take a closer look at each of them. So let's start with the astrocytes then. The astrocytes, we can see those quite nicely in the picture. The picture here. Imagine it, or it's on your laptops if you've got it. Here we go. So in the picture here, we can see a blood vessel, as you might find in the central nervous system. And surrounding the blood vessel, we've got these astrocytes. And the astrocytes form what's called the blood-brain barrier. So again, you might have heard of the blood-brain barrier. The blood-brain barrier is there to provide a barrier that allows some things into the central nervous system but stops other things from getting in. So for example, small substances like oxygen, carbon dioxide, glucose, lipid-soluble substances, so like alcohol, these can cross easily from the blood into that nervous tissue. So they're able to have effects on our brains on our nervous tissue. Large molecules, on the other hand, for example, lots of different medications and drugs, these can't get across the blood-brain barrier. And that's why it can be very hard to treat some conditions because we just can't get the medications where it needs to be. So that's our astrocytes, which we can see in the picture here. The next one are oligodendrocytes, if you're good, thank you. If you have one, thank you. So oligodendrocytes, you might have heard of Schwann cells. Schwann cells are the cells, the equivalent cells in the peripheral nervous system. So in the peripheral nervous system, Schwann cells produce this fatty substance called myelin that wraps around the axons of the neurons and speeds up electrical conduction. In the central nervous system, it's not Schwann cells that do this, but it's oligodendrocytes. They're doing exactly the same kind of thing. They're forming and maintaining those myelin sheaths around the axons to help speed up conduction of our electrical impulses. So oligodendrocytes in the central nervous system, Schwann cells in the peripheral nervous system. Appendimal cells, these are found as the lining cells of the ventricles. Next week, when we look at anatomy of the central nervous system, we'll look at ventricles, a lot more detail. So we'll take a look at them. It's in the ventricles of the brain that we produce our cerebrospinal fluid. So we're able to produce cerebrospinal fluid and that is done by the appendable cells. So they're producing that fluid, the fluid that bathes our brains and cushions it to stop us rattling around in our skulls. Microglia are our dustbin then. So these are our phagocytes that are able to clear up any debris in our nervous tissue. So we want to get rid of old dead cells. We want to get rid of any inflammatory molecules. So we're able to phagocytose and clear them out the way. So as you can see, our glial cells or our neuroglia are super important, really important when it comes to the function of the nervous system. Neurons are probably the part that you're more familiar with. And this picture here I'm sure you're quite familiar with as a typical neuron here. So our neurons are what we call our nerve cells. The nerve cells are called neurons. Some people drop the E at the end so it's a neuron without the E. Some people say neuron, some people say neuron. I don't mind, whatever you want to do. So neurons are nerve cells and we can see here at one end we've got our cell body. Now the cell body is where we have the nucleus. So the cell body is an enlarged part of the cell. It's where we have the nucleus and we have lots of organelles. From that larger cell body, we then have one extended axon. So we have a nice long axon in the picture here and it's down this axon that will have our electrical conduction. The electrical messages need to be able to transmit from one end to the other end. From the cell body you can see lots of little projections. These are called dendrites. We'll look at those a bit more later on. They're gonna help us collect information and bring it together. It all gets a bit complicated. Bringing information together from multiple neurons to decide whether or not we send that signal on or not. The axon hillock is where the cell body meets the axon and this is where our electrical impulse is generated. As I said, neurons can't divide. Let's swap to the walkie-talkie. I appreciate you coming out for it. Thank you. All right. So neurons then, the cell body of the neuron, let's turn the volume up a bit. The cell body is the bit that contains the nucleus. So in our cartoon up here, here's our cell body and we can see it's got the nucleus in the center. Now this forms what's called the gray matter in the nervous system. When you think about the nervous system, have you heard of gray matter and white matter? Hopefully something you've heard of before. Let's look at the cross section of the brain here. It's a cross section that's been taken kind of slicing from ear to ear. Can you see around the edge of the brain, it's a slightly darker color compared to in the middle. So around the edge of the brain here, this is our gray matter. Okay, so the gray matter forms a small layer surrounding the outside of the cerebrum. Okay, so it's the periphery or the outer edge of the brain. If we look down to the spinal cord, again, this is the cross section, it's been taken through the center of the spinal cord, you get this kind of butterfly in the middle and the gray matter is in the middle. It's in that butterfly. So the gray matter is where the cell bodies are, it's where the nuclei of all those neurons sit, and those neurons, the nuclei are found in the periphery of the brain, but the center of the spinal cord. Okay, so if we look at this picture here, can you see this circle here, this represents the cell body, the nucleus, and the neuron, the axon, comes all the way down to the spinal cord. We have a little synapse to a second neuron, which then goes out to a muscle. So where we have the cell body, where we have the nucleus, is in the outside of the brain, up at the top. And where we have the synapse is where we also have another cell body, we have another nucleus, because the synapses are gonna happen onto the cell body. And then the message goes down it, and from this end it will go onto another cell body. So we have nuclei in the gray matter of the brain, the edges, and we have nuclei in the gray matter of the spinal cord, which is in the middle. Okay, making sense, just about. The axons then, so we know from our cartoon, the axon is the long projection down which that electrical impulse is going to be transmitted, and this forms the white matter of the nervous system. So we've got in the cartoon here, we've got the gray matter at the edge of the brain, where that cell body is, the nucleus is, and then where the axon travels through the brain, that's all white matter. It's colored white, and the reason it's colored white is because of that myelin sheath. The fatty myelin is whiter in color, it's paler in color. So it looks a paler color. So we see the white matter in the center of the brain, coming down through the center, and in the periphery around the edges of the spinal cord. So these axons travel down around the edges of the spinal cord, and then go into the middle where they want to form a synapse, where they want to connect to the next neuron. So cell bodies contain the nucleus, they form the gray matter, axons carry the impulses and form the white matter. Tracks are what we call bundles of axons in the central nervous system. So we don't see just one axon coming down this little pathway here, we'll have a whole bundle of axons traveling together, and when they travel in groups or bundles, it's known as a tract. In the peripheral nervous system, when axons are bundled together and travel in a group, that's called a nerve. So a nerve is something you're quite familiar with, you've thought about that before lots, I'm sure. It's a group of axons, a group of neurons, all traveling together in a sheath. So a bundle of axons is a nerve in the periphery, a bundle of axons in the central nervous system is called a tract. How do we get signals to travel fast enough around the body? Well, there are two different ways we can do this. Invertebrates have chosen one way, and we have chosen a slightly different way. So what invertebrates like a squid do, is they make their axons fat. So a big diameter, the fatter the diameter, or the bigger the diameter of your axon, the fatter your axon, the faster the signal will be. So in a giant squid, the axons can be up to a millimeter in diameter. You'd be able to see the axon of a neuron by eye. Okay, so they're that big, so that speeds up their conduction. We don't have axons that big, otherwise we'd be enormous, wouldn't we? So instead, we speed up our electrical conduction by insulating the axons with a fatty substance, with myelin. And you can see that in the cartoon here. These little bubbles represent myelin. This is our myelin sheath. And this insulates the axon. If you think about insulating any kind of electrical wire, so we don't want electric shocks, we can insulate them. And it means the electrical message jumps from one node to the next to the next. So it doesn't have to travel all the way along, it can jump its way along instead. So we can speed up our conduction that way. So let's think a little bit more about myelination then. Oligodendrocytes are the cells that do myelination in the central nervous system, Schwann cells in the peripheral nervous system. The cartoon here, it shows what's happening. So in yellow is our axon. And in blue, this is our Schwann cell or oligodendrocyte. So it wraps around the axon. But it doesn't just wrap around it once. It coils, it like rolls it up so it's twisted around it over and over. Can you see how it's coiled up inside the Schwann cell or inside the oligodendrocyte? And then the oligodendrocyte or Schwann cell produces this fatty substance called myelin between the layers. So between those coils, it's secreting a fatty substance and that provides electrical insulation. Not only do our Schwann cells and oligodendrocytes provide that electrical insulation, they also provide nourishment. They also feed the neuron. They help provide nourishment and nutrition to the neuron as well. So yes, it helps with conduction, so fast conduction from node to node, but also about nourishment and helping keep neurons healthy. Here's our dendrites then. So dendrites are these projections coming out from our cell body. From the cell body, you'll have one long projection, usually one, sometimes one in each direction. Sometimes nerves or neurons can be bipolar, having one going in each direction. But most often they have just one long axon, but they have other branching projections which help increase the surface area to receive incoming messages. So in yellowy color is our main neuron that we're thinking about here, but in green is all the incoming messages, all the incoming neurons which are then synapsing or making connections with this neuron. So you could see that we could have either a few messages coming in from different neurons, or you could have thousands of incoming neurons providing an input into this yellow neuron which will then ultimately decide does it send the message forward? Does it transmit it onwards? So lots of short processes for incoming messages, often branching. In sensory neurons, they help form the sensory receptors, so things like mechanoreceptors, sensing mechanical movements. In motor neurons, they help form part of the synapsis. Later on, we'll see how this pulls things together, how it coordinates the message that's coming in and decides if it's sending a message onwards. I think we definitely need a one-minute break. Let's take a one-minute break. We've covered a lot of anatomy of neurons, and we're heading into some pretty heavy physiology next. So one-minute break, take a breather for me. All right. So hopefully we're all now quite happy and comfy with our structure of our neuron. We've got our cell body, where the nucleus is. We've got our dendrites receiving incoming messages. We've got our long axon down which we need to transmit our electrical message, or nerve impulse. And then we're going to need to send that message on from the end of one neuron onto the next neuron. So we need to get that message across a gap from one to another. And we do that through chemical conduction. So rapid transmission of nerve impulses. Some neurons are able to initiate nerve impulses, for example, sensation. When we have a sensation of touch, those neurons detecting touch are able to initiate messages. Other neurons are just sending the message on, receiving it, sending it on. So some are just relaying the messages. Transmission is both electrical and chemical. The electrical bit is the bit that's going down the axon, and these electrical impulses are known as action potentials, action potentials. The chemical bit is the bit that happens between adjacent neurons, between one neuron, neuron, and the next neuron. When it has to jump across the gap, across the synapse, this is our chemical conduction. So we're going to break it down into the two parts. We're going to start by looking at action potentials and electrical conduction, and then we'll move on to our chemical conduction. I've got a really nice one-minute animation. Well, it's a bit dramatized, but therewith, okay? It's quite... It's all right. Let's give it a quick whirl. I'm going to kind of narrate over the top, so we'll see if it does the music. If it's muted, we'll do the really dramatic one. So we can see, if I can hear us, these are action potentials, so the movement of one across the membrane. So we're going to move it, okay? So we're going to change the charge across the membrane. That electrical message, that wave of moving things, moves all the way. It gets to the end. It's going to cause these, of course, containing neurotransmitters to be released. So here, the red dots are that they bind to a receptor, and there's a lot to think about. Let's go through it again. So net-weloming trigger, it's standing in the middle, it's going to pulse down the axis, it's going to pulse in the movement of the membrane. So it triggers release to these, the granules. So it's released these little red neurotransmitters. They bind to channels, opening the channels. It's a little red neurotransmitters of the channel. It opens, it's going to change the next neuron. It's going to change the charge again, sending the message onwards. When I started drinking warm water to help... Drinking warm water, okay. Right. There is a huge amount to try and take in from that video. Let's see if it makes more sense in about an hour's time when we've been through all the detail, okay? But this is what we're trying to get our heads around today. What happens when the incoming signal comes in? What is that electrical transmission? What is happening to cause that wave down the axon? What happens at the end of the axon to make the signal jump from one neuron to the next? Okay, so electrical impulses. An impulse or action potential is a wave of movement of ions across the nerve cell membrane. So it's a movement of ions, charged ions across the membrane. So we can see in the picture here, most of the time the inside of a cell is negatively charged relative to the outside. So the outside is more positive, the inside is more negative. But here, do you remember in that cartoon, all those positive ions went inside, they moved inside, so it switched the polarity. It made it more positive on the inside, more negative on the outside. And that moves as a wave down the neuron, okay? So we go back the other way, so it's gonna move, it's sent all the positive, or a load of positive ions inside, making it more positive inside at that bit of the membrane, which then carries on down the axon, down the axon to the very end. So this is going to involve a really coordinated, well-organised, tightly controlled opening and closing of ion channels. We only want to let certain ions move in, certain ions move out, and we're very specific about the timing of it all, okay? The two key channels that we're gonna focus on are the sodium channel, and the sodium channel, and the potassium channel. These are both positively charged molecules, or ions. Okay, so Na plus, K plus, they're both positively charged. But you'll see in a moment, they move in different directions. Do you remember, right? Back to the beginning of the module, so think back to about last October, week two, we started looking at physiology, and we've looked at things like the sodium-potassium pump. Does that ring bells, the sodium-potassium pump? We talked about the fact that inside animal cells, there is lots of stuff. There are lots of ions, there are lots of proteins, and these things pull water into the cells. So all of these things inside is gonna pull water inside. And if we're not careful, the cell's just gonna expand until it pops. And we don't want that to happen. So to prevent the water from coming inside and popping the cell, we need to have our sodium-potassium pump. What the sodium-potassium pump did was it pumps three sodium ions out and swaps them for two potassium ions coming in. So it sends three sodiums out, two potassiums in. And do you remember, I've said it a million times, water follows sodium, yeah? Remember that good old one from, we talked about it back at the beginning of the module? We covered it again in renal physiology, water follows sodium. So the reason we don't explode our cells by pulling too much water in is because we pump sodium out, and some of the water will follow that sodium. So our cells don't expand, expand, and pop. Our sodium-potassium pump uses a huge amount of energy. It's why we need to keep making ATP to keep these sodium-potassium pumps going. But because the sodium-potassium pump is constantly pumping sodium out, constantly sodium is being sent out of the cell. It means that at rest, our sodium concentration is higher on the outside than it is on the inside. So sodium is higher outside and lower on the inside. Potassium is the other way around. It's much higher on the inside and lower on the outside. So our sodium-potassium pump is maintaining high sodium outside, low sodium inside. But if we open a sodium channel, the sodium will go down its concentration gradient and it will move from outside to inside. So that positively charged iron sodium, if we open a sodium channel, it will just flood inside. Sodium-potassium pump keeps pushing it out, but if we open another sodium channel, whoosh, it will come inside. Think of the cartoon of the axon and the action potential, those positive ions being moved inside. That's what's happening. We're opening sodium channels, whoosh, the sodium floods inside. Makes it more positive on the inside. So that's what this graph here shows. This is a graph showing an action potential. At rest, the inside of a neuron, is negatively charged, about minus 70 millivolts. So it's at rest, the inside, more negative. As we know, sodium is higher on the outside, potassium is higher on the inside. That sodium-potassium pump is setting that up. Sodium high outside, potassium high inside. So what happens when an action potential is initiated, when it gets triggered, is it opens voltage-gated sodium channels. These are sodium channels, so channels that allow sodium through, but they're under the control of voltage. They're voltage-gated. They open when they get an electrical impulse. So an electrical impulse opens those sodium channels, and sodium, which we know is positively charged, follows its concentration gradient from high to low, and rushes inside the neuron. If something positive goes inside, we're going to go from a minus number to a more positive number. So it causes the voltage inside to increase, to become more positive. This is called depolarization. Depolarization, when it becomes more positive inside. So a wave of depolarization, the inside of the neuron becomes more positive because more sodium ions have rushed inside. And this wave effect spreads down the axon in milliseconds. It's super, super quick. So if we look at the x-axis on here, that action potential going up and down, it's done it in about a millisecond. It's really, really quick. Before we get this full action potential, we have to get over what's called a threshold. So initially, a few sodium channels were open, and a few sodium ions will come inside the cell. So it'll get a little bit more positive. It will go, say, from minus 70 to minus 60. But it hasn't yet reached the threshold. If it doesn't get to minus 55, it just kind of gives up, drops back. It will only trigger the action potential if we get to minus 55 millivolts. So enough sodium has to move in, flow inwards to get to minus 55 millivolts, and then it will trigger the rest of the action potential. If it doesn't get to minus 55, it fails, and that action potential just dies. It just stops. It fizzles out. Let's finish off the next two sides, I think, and then we'll take a proper break, okay? And then I probably will go over this again because I think this is all quite complex stuff. So we know that sodium flowing inwards, we received an action potential, electrical impulse, that has opened voltage-gated sodium channels. Sodium now flows in down its concentration gradient. It's got more positive inside. In order for it to go back to reset, to repolarize, we're gonna open some potassium channels now. So the potassium channels now open. Potassium was higher on the inside than it was on the outside. So when we open a potassium channel, the potassium's gonna go from inside to outside. So we've now got some positive going from in to out. What this does is it causes a wave of repolarization. So there's less potassium on the inside, making it more negative again. So our voltage becomes more negative. So it got more positive from the sodium rushing in. It's got more negative from the potassium rushing out. We often get an overshoot. This is called a refractory period. This is where we get hyperpolarization, so more potassium goes out than anticipated. It takes a while for the potassium channels to close down again. And it's quite interesting because in this period, it's now got even more negative. So in order to send another impulse, to send another wave of activity, the axilon has to go from right down here back up to minus 55 again. Remember, we can only send another impulse if we can get to minus 55. So from down in this refractory period, it's much harder to get to minus 55. It means that we have to have a much stronger impulse, a stronger stimulus, to trigger a message quickly again. Otherwise, we have to wait for it to get back to the resting state. How's it gonna do that? The good old sodium-potassium pump. Swaps them all back to where they went meant to be again. And then it's only a small gap to go from minus 70 to minus 55. But down in this refractory period, it's like a pause button. It means that it can't send the messages back the other way. They're only a uni-direction. It means that we can't send messages too strongly unless we have a really strong stimulus, okay? So it just means that we can't overload the nervous system unless it's a really strong stimulus. So as I said, to get back to the resting state, it's the sodium-potassium pump that gets us there again. Three sodium out, two potassium in. It will reset us back to our equilibrium again until we get another action potential, another message to say open the sodium channels. Sodium will rush in, potassium will rush out and another wave goes along. Can you think about that cartoon we saw in the video? It was a wave of positives going in and out. So it's a bit misleading because it looked like it's the same positive thing going in and out. Whereas now you know that it was sodium going in, potassium going out, and then in the background they get balanced again. So it is a simplified cartoon, but it does help us a little with our understanding. Okay, Nernst equations are horrible maths, so I think we have a 10-minute break before we get to that point there, yeah? So let's take a break by the clock till five past, okay? Five past by that clock. So I thought before we carry on, I'd just do a quick recap of some of what we covered because I think it can be quite confusing and quite complicated, this one. So I've added some notes to the whiteboard as well. I don't know if it's big enough for you to see, but hopefully it helps. So here is our cell. We've got our sodium-potassium pump sending three sodiums out, two sodiums in, and that helps to set our concentration. So the concentration, square brackets means concentration. Concentration of sodium on the outside is about 140. Concentration of potassium is about four. Concentration of sodium on the inside is about 14. Concentration of potassium on the inside is 140. So that's what our sodium-potassium pump is maintaining all the time. But if we then open a new channel, so if we open a sodium channel here and allow sodium to rush in, it's gonna go from 140 to 14. It's gonna go down its concentration gradient. So we get these positive ions rushing inside when these channels are opened, only when the voltage-gated sodium channels are opened. So we saw that when we get an initial trigger, so we receive some sort of impulse, some sort of message. We haven't really talked about what that is yet. I'll come back to that later. Some sort of initial stimulus. It's gonna open up some of those sodium channels. Sodium being positive is going to take this from a minus number and make it more positive. If it doesn't reach minus 55, nothing happens. It goes no further. But if we can reach minus 55, that then triggers lots more of these channels to open because they're voltage-gated. So once we get to minus 55, we're gonna open loads and loads of these sodium channels and loads of sodium is gonna flood inside. So we get depolarization. We then get, which is very quick, sort of about a millisecond to get full depolarization happen. At the same time, potassium channels are open, but they're slow to open. So they're triggered at the same time as the sodium, but they're slow to open. The sodium ones open quick and let sodium start moving. Potassium ones are slowly opening. Only when they're open now, the potassium is gonna go in its direction. So let's add a potassium channel and the potassium is high on the inside, low on the outside, the potassium is going to go the other way. So now we're taking the positives, we're making it less positive inside because we're taking the positive outside. Less positive means we're coming down the other side of this curve, so that's our repolarization. It often overshoots into a refractory period before the sodium-potassium pump rebalances us out at the resting state again. Once we're back at the resting state, we could trigger another action potential. So we get waves of them traveling down the axon. If we wanted to trigger two action potentials really close together, it's much harder to trigger it from a more negative number. It's harder for it to get to minus 55, so we need a strong stimulus to be able to trigger them quickly in quick succession. Nernst equations. Good old Nernst equations. These can be used to calculate the membrane potential. So this is our Nernst equation here. EI stands for the iron equilibrium potential. It's all in the notes bit of the slides. If you've got the PowerPoint open in front of you, it's in the notes. The EI is our iron equilibrium potential, which is our membrane potential, but for different ions. Depending on what iron we plug in, we're gonna get a different membrane potential. 2.3 is a conversion factor to go from a natural log to a log to the base 10, so we're gonna add in that conversion factor. R is a gas constant. T is temperature in kelvins. F is Faraday's constant, which is the electric charge in one mole of electrons, and Z is the charge of the iron we're talking about. Concentration on the outside, concentration on the inside. So what we can do is plug in these numbers for our two key players. We've got sodium and we've got potassium. Here are our concentrations. I think we're gonna start with potassium. Potassium on the outside is four. Potassium on the inside is 140. So at rest then, the membrane potential for potassium is 2.3, that's been up there. RT over ZF is a constant. It's a constant times the temperature, which is body temperature, so it doesn't change, divided by a constant. So it doesn't really change much at all. So that's 26.7, and then we've got our log concentration on the outside, concentration on the inside. So if we plug all of this in for potassium, we get minus 94 millivolts. In other words, it's not far off this baseline value here on minus 70. This tells us that it's potassium that sets our resting potential, our resting membrane potential. So potassium is setting the baseline. Let's see what happens when we plug in the sodium numbers. We've got our sodium numbers as well. Let's plug in the sodium and see what happens on what values we get the sodium. So for potassium, we get minus 94. In other words, potassium sets the resting membrane potential of minus 70, somewhere between minus 70 and minus 90. See, it goes down to sort of minus 90 when it goes in that refractory period here. Okay, let's see what happens with sodium then. It's the same equation, 2.3 times a constant, times by the log concentration on the outside, concentration on the inside. So for sodium, 2.3 times 26.7 log, 140 is our outside concentration, 14 is our inside concentration. What does it all come to? Plus 61 millivolts. So we now get a positive number. In other words, it's the sodium that's going to drive it to become more positive. So sodium triggers the depolarization, whereas it's the potassium that triggers us getting to that resting state. Whether it's at the start or whether it's at the end, potassium brings us back to the resting state. Sodium is the one that drives it to be more positive. So although it's two positive ions that are moving, one is making it more positive, one's making it more negative. Not fun stuff to think about, is it? Don't get too bogged down in it. I don't expect you to learn the equation. Don't expect you to, I do expect you to remember back in week two, I told you I wanted you to learn the concentrations of certain ones. I told you which ones to learn. Sodium, potassium are on that list. So I do expect you to know things like that. But the Nernst equation, it's not going to come up, okay? Or if it does, I will give you the Nernst equation, okay? The only reason I go through the Nernst equation is to help explain the actual physics, which is not my strong suit at all, as to how these action potentials are happening. Okay. So we've talked about how this message travels down the axon. Let's, before we go to initiation, let's go back to that YouTube video. Not watch her. Let's go back one. Let's watch this one again. And try and put that all together. So we've got some of that. Angels. Cross the membrane. When it gets to the end, we haven't got to this bit yet, have we? We've got release of neurotransmitters, binding to channels, enter the next neuron, and start the whole thing off again. Okay, let's pause there. Is that video making a little bit more sense that time through, having seen a bit of the detail, yeah? Okay. So what we've lost over is that initial stage. How do we trigger the action potential in the first place? How do we actually initiate it? Well, the action potentials are initiated at the axon hillock. The axon hillock, the join between the cell body and the axon. It's here that the decision is made whether the message is gonna be passed on or not. This is where the threshold has to be reached. So at the axon hillock, it's measuring, the action membrane potential is being monitored. If it gets to minus 55 at that axon hillock, it will then open up all of the channels, all of the sodium channels that aren't yet open. They will all be opened, allowing then us to flood the cell with sodium and we get our full action potential. So that's an all response. If the threshold is reached, all the channels get opened, we get a full action potential. If the threshold is not reached, then we get the nothing response. We don't reach that minimum level so therefore there's no action potential and it just fizzles out. So this is why nerve impulses are described as all or nothing. We get a summation of effects coming into the axon hillock here. If it gets to minus 55, we get all. If it doesn't, we get nothing. Single action potentials are super fast, less than a millisecond. We've already seen the idea of how this moves down the axon so we get this wave effect of it moving down. So it sweeps along the axon, opening more and more sodium channels as it goes and this is called simple propagation. So this is what's happening in our giant squid. Okay, nice and simple and the giant squid, it's just traveling straight down the axon. We've got one-way transmission because of the time for repolarization. It means it can only go in one direction. It can't go back the other way. The thicker the axon, the faster the conduction. That's how giant squids get around it or they've got these one millimeter thick axons. But we already know that we do it slightly differently. Diameter still matters for us, absolutely. The fatter our axon is, the faster the message will go and we'll see that's important in a moment. But the other thing we do is use myelin, these fatty sheaths that allow the movement of the ions. So here, again, we've got this idea that, this is the one where I think it's got the error, isn't it? So remember it's becoming more positive on the inside. So I think the one they should have colored in is actually that one and that one and that one. They've colored in the wrong one in the picture. In the newer editions, they might have updated it and corrected it, but in the old one, they have colored in the wrong one. But you can see the idea that it's moving as a wave jumping from one side of a fatty sheath to the next side of the fatty sheath. So it jumps and jumps and jumps along the axon. It doesn't have to go along the whole thing, it can skip its way along. So these gaps are called the nodes of rambeae, nodes of rambeae in between each of the Schwann cells or oligodendrocytes. Wave of depolarization passed along the mind and sheath and seems to jump from node to node. This is called saltatory conduction. Saltatory conduction. So simple conduction, giant squid. Humans, saltatory conduction. Much faster. Okay. So putting this into a little bit of applied action then. When you put your foot in a hot bath of water, imagine you've run yourself a super hot bath, you put your foot in. Why is it that you can feel the bottom of the bath with your foot before you feel the pain from it being too hot? You know when you run a bath that's too hot? And you put your foot in and you can feel the bottom and then afterwards you go, ow, and you might use some more choice words, but you put your foot in for a bit first and you felt the bottom. Often you've even moved your leg out of the way before you've then gone, ow, afterwards. So why is it that we can feel the bottom before we feel heat or before we feel pain? What's going on there? But it's all to do with speed of conduction. So conduction of nervous impulses is dependent upon the diameter of the axon. Remember our giant squids, where they're really wide diameter of their axon, so the wider the axon, the faster it will go, and also myelination. Myelinated axons are faster. So this table here shows the different types of neurons or different nerve fiber types that we have. Don't worry too much about the fiber type names at the minute, we'll come back to those later. But notice that we've got different diameters. So some of our nerve fibers are fatter than others. Okay, so some are fatter, some are thinner. Some are myelinated, some are not myelinated. And this changes the speed that these neurons are able to transmit the messages. So remember the fatter ones will be faster. Myelinated will be faster. So these top ones travel at 100 meters per second. And the neurons which are fattest and myelinated are our motor neurons, our movement ones. So the fastest messages in the body are the ones that tell us to move. The next fastest ones, they're not as fast, but they are still myelinated. These move at 50 meters a second. These are for touch. So touch is not as fast as movement. The next one's down, not as fast, still myelinated 20 meters per second. These are for special type of sensors. Don't worry too much about those. The next one's down 15 meters per second. This is for fast pain, so a type of pain, and for temperature. So if we look at these ones here, you can see that movement and touch are faster than pain and temperature. So touch is faster than temperature. I can touch the bottom of my bar and feel and mentally understand touch before the message for temperature gets to my brain. In fact, some of it is so fast, the message for touch and then temperature and then movement happens so fast before I consciously even thought, what was I doing, I've moved out the way. Unless you're really dark and you put your foot in it, you're like, no, I want a scalding bath, but most of us take our foot out and run some more cold. So movement is the fastest. Touch is next fastest. Skip the muscle spindles, don't worry about them for now. Fast pain, which is when we get a sharp pain or a burning type pain and temperature. Autonomic messages, pretty slow, but the slowest of all, these ones here, super thin, unmyelinated, this is for slow pain. Slow pain like dull, achy, inflammatory pain. When you sprain your ankle, you've got a bit of inflammation. Okay, so this type of pain travels really slowly, much, much slower. Are we happy with the idea of speeds of pain, speeds of transmission? Some messages travel faster than others. We'll come back to that later or possibly the next week when we talk about things like the different nerve types, sensation and motor and so on. We'll come back to this again. Got more maths for you then. How fast are the fastest nerve impulses? So motor neurons. We know that they travel at 100 meters per second. Do they travel at 30 miles an hour, 70 miles an hour, to 20 miles an hour or 660 miles per hour? What do we reckon? We could do the maths if we had to, couldn't we? I'm sure you could convert from per second to per minute and from per minute to per hour. So we can get meters per hour, then we need to convert to miles, which we could look up how many miles, meters there are in a mile, couldn't we? We can do all of that. So there are 1,609 meters in a mile. So if it's 100 meters per second, then it's 100 times 16 meters per minute. Times it by 60 again, gives us per hour. Divide that by 1,609. Our motor neurons are sending messages at 224 miles per hour around your body. That's the speed things are going at. Okay, it's pretty impressive, isn't it? This is the body doing amazing stuff, okay? 224 miles an hour, that's amazing. Okay, the tricky thing that we've got is that every action potential, oh, how far back we gotta go? There's a picture. Every single action potential is the same size. Each of them follows exactly this graph because each of them, if it gets to minus 55, it opens up every sodium channel, lets them all in, and then has to reset again. So if every single action potential looks exactly the same, how do we perceive the difference between something really quiet and something really loud, something really soft and something really hard? How is that happening? If the size of the action potential is identical, how do we interpret them as soft or strong? So it's all about the frequency of these action potentials. We can't make them bigger or smaller, but we can change how back to back, how rapidly they fire. So this is all about coding information. If we look at the graph here, if we've got a stimulus, that stimulus might be touch or it might be sound or it might be brightness. If it doesn't reach the threshold, we get no action potential. If the stimulus reaches the threshold a little bit, we start to get action potentials and they'll sort of follow each other, we'll get one after another. But if we have a stronger stimulus, then they're triggered much more quickly. Remember that refractory period where you had to have a strong stimulus to get the trigger to happen within the refractory period because it's got to go from minus 90 to 55, not just minus 70 to minus 55. So if we have a strong stimulus, we can get them much closer together. And this is what our central nervous system receives. And this is what it then converts to either volume, brightness, touch, pain, all those different sensations. They're all coded by action potentials. But how the brain interprets them, that's the magic bit. How it interprets these things in different ways. So a loud sound will have more frequent action potentials, a quiet sound would have less frequent action potentials. So a summary for action potentials, neurons are signaled by action potentials. Action potentials, generation depends on arresting membrane potential, which is established by our sodium potassium pump. Primarily potassium fixed the baseline. We then have an all or nothing event. If we get to minus 55 at the axon hillock, it opens up all of the other sodium channels allowing loads of sodium to flood in. So initiated by a rapid increase in sodium permeability, which depolarizes, and then a slower increase in potassium permeability, which repolarizes. It's the frequency, not the size that gives us the strength of our perception, how much we perceive it as. Fun stuff, action potentials, aren't they? Our next section then is chemical conduction. How does the message get from one neuron to the next? Let's take 30 seconds before we go into chemical conduction, okay? 30 second decompression. Okay, so we've learned about how the message travels down a single axon from the cell body to its end. And then the message now needs to jump from one neuron to another. So this chemical conduction to convey the impulse from one neuron to the next. And it's moving across a gap called the synapse. So two neurons meet at the synapse. You have a pre-synaptic neuron, so that's the incoming neuron, and a post-synaptic neuron, that's the outgoing one. And the chemicals that cross that gap, these are called neurotransmitters, neurotransmitters. So in the cartoon here, here's our pre-synaptic neuron. In vesicles, we've got our neurotransmitter. It's gonna be released into the synapse, the gap. Binding to receptors, which typically open channels, and then that opening of channels is gonna start a signal, an impulse in the post-synaptic neuron. The neurotransmitters which get released into the synapse, they actually get degraded quite rapidly. So they don't hang around for a long time. They're degraded quite quickly. So in order to keep a signal going, you need to keep releasing more and more neurotransmitter. If you release a bit within quite a short time, it will be cleared out and the message stops. So you have to keep releasing more and more. There are more than 50 different neurotransmitters, and these include acetylcholine, and you should have heard of acetylcholine. It's the one for our somatic motor function. So Dr.

So Dr. Sam talked about acetylcholine when he talked about how muscles become activated at the neuromuscular junction. So we have a nerve coming into a muscle fiber, triggering it to contract, and it was acetylcholine as the neurotransmitter that did that. But we have others such as glutamate, GABA, noradrenaline, adrenaline, dopamine, and serotonin. We'll look at those in more detail in a moment. So what's happening then when we have these neurotransmitters? Neurotransmitters are able to bind to receptors on the post-synaptic neuron, on the post-synaptic neuron, and they open up channels. We saw it in the video, didn't we? The neurotransmitter bound, and it opened the channel. So here, we've got an example with acetylcholine binding to its receptor, which is also a channel. So when it binds, it opens the channel, and sodium, back to good old sodium, is able to flood into the cell. So when acetylcholine binds to its receptor, it opens the sodium channel, and sodium enters the neuron, the post-synaptic neuron. We know that when sodium comes inside a neuron, it's going to make it more positive on the inside. What does that do? It starts to activate the new action potential. If we can get it to minus 55, if we can make it more positive, so it goes to minus 70, if it can reach minus 55, boom, the next wave happens down the next neuron. So that's nice and simple, isn't it? Message comes in from one neuron to another, open sodium channels, sodium floods in, makes it more positive on the inside, triggers an action potential. But it's not as simple as that, darn it. We also have other neurotransmitters that can open other channels. For example, the neurotransmitter GABA, the channel that it is linked to is a chloride channel. Now chloride is negatively charged. So when GABA is released across the synapse, when GABA causes chloride, negative ions to go inside the postsynaptic neuron, it makes the inside more negative. If it's more negative, it's not going to reach that threshold of minus 55. It's going to make it harder to get to the threshold. So GABA is what's known as an inhibitory neurotransmitter. It's a calming neurotransmitter. So some neurotransmitters are excitatory. They trigger action potentials. They excite the nervous system. And some neurotransmitters are inhibitory. They calm the nervous system. And having that balance is what is really important. I glossed over the fact that mechanorestinoxys can also open some channels. So physical touch, what's that doing? It's opening up ion channels, triggering action potential. Okay, so acetylcholine is an excitatory neurotransmitter. GABA is an inhibitory one. So what's happening then if we look at acetylcholine? As acetylcholine opens up the sodium channel, it's going to become more positive inside. If it becomes more positive, it's getting closer to minus 55. That little bit of more positiveness or less negativeness opens some voltage-gated channels. When we open the voltage-gated sodium channels, more sodium comes inside. It gets closer to minus 55. That opens more sodium channels. It gets even closer to minus 55. If we get to minus 55, it triggers all of the other sodium channels to open. So this is our all or nothing. Once, initially, it's just little by little, but once we get to minus 55 millivolts, boom, the whole lot open, sodium floods inside and it triggers our action potential. If we don't reach the threshold, nothing happens and it fizzles out. All or nothing. So here are some neurotransmitters for you. We've got adrenaline. So adrenaline is a hormone and a neurotransmitter. It's not just a neurotransmitter. It acts as a hormone as well. You'll be familiar with it from our flight and fight response to our stress response. We've also got noradrenaline, which is related to adrenaline. Now this one, it's all about concentration and alertness. So we produce this neurotransmitter when we're concentrating. It helps us with our concentration. Dopamine is involved in pleasure and reward. So if you do something that causes a dopamine response, a dopamine release, it triggers reward centers in the brain and therefore we want to do it again. Now all of us in the room will get dopamine hits from different activities. Some of you will get a dopamine hit from baking. Some of you will get it from skydiving. Some of you will get it from drugs. Some of you will get it from hanging out with your mates. We all get dopamine from different things. But if we get dopamine, we like it, so we do that thing again. It makes us want to do stuff again and again. It kind of links into addiction and that kind of behavior as well. Okay, serotonin, you might well have heard of serotonin. It's a mood neurotransmitter, often talked about as a happy one. So it's all about mood. Again, reward and arousal. GABA, we met GABA earlier. That was our calming neurotransmitter. So GABA is the main inhibitory neurotransmitter in the brain. It's the main inhibitory one. It's the one that helps calm our brains down. If we were firing neurons all the time, it's not good. Our brains can't cope with that. We need some calming in there as well. Acetylcholine is for learning the motor function. It's in the neuromuscular junction, but it's also for learning. It's also for memory. Glutamate is the main excitatory neurotransmitter in the brain. It's important for things like memory and learning, and there are thought to be links with both Alzheimer's and epilepsy for glutamate. So if we have too much or too little. Endorphins, these are our feel-good factors. We often release these when we're in pain to try and get through the pain. So again, involved in pleasure and feelings of euphoria. So different neurotransmitters flying around, crossing synapses, some of them making the inside of the next neuron more positive, some of them making it more negative, having different effects. So some neurotransmitters are excitatory. They trigger action potentials. For example, acetylcholine and glutamate. These neurotransmitters both open sodium channels. They let sodium flood inside. It becomes more negative, and that's going to help trigger an action potential. So they are known as excitatory postsynaptic potentials. EPSPs, excitatory ones. On the other hand, some neurotransmitters are inhibitory. So GABA, we've met, but also things like opioids. So things like morphine, heroin, codeine, that sort of thing. Acetylcholine can also be inhibitory. So it's excitatory in motor muscles, skeletal muscles. But acetylcholine is inhibitory in cardiac muscle and smooth muscle. So it has different effects depending on which tissue it's in. GABA opens chloride channels, making it more negative inside. If it's more negative, it's going to be harder to get to that minus 55. So that's an inhibitory neurotransmitter. It causes an inhibitory postsynaptic potential, an IPSP, inhibitory one. Inhibitory ones are really important for things like startle. OK, so if I clap something, you know, most of you jumped a little bit. If I do it again... Anyone jump anymore or have you stopped jumping? Might be jumping a little bit, a bit loud, isn't it? But we get desensitized. We get desensitized because these inhibitory postsynaptic potentials start to kick in. Otherwise, we'd be jumping all over the place all the time. Our brains, our nervous system needs to be able to calm down as well as be stimulated. So it's important for desensitizing against things like startle. Do you remember right at the beginning we talked about dendrites? Yeah?

All of these incoming messages. Well, this is where that now starts to make a bit more sense. In this cartoon here, in green, all the incoming synapses from one neuron coming in, all the ones in green are excitatory. So excitatory is in green, whereas in red is all the inhibitory messages coming in. So this one neuron is receiving hundreds of incoming synaptic messages, some of them saying, get excited, some of them saying, calm down a bit, and overall, that's going to cause an overall effect. Some of them are sending sodium in, some of them are sending chloride in. So they're sending different things in and out of the cell, and it's the overall effect that matters. It's what's the summation. This is called summation. When we add together all those different charges, do we end up with it being positive or negative on the inside? What is the overall charge? So this gives us that overall threshold. And you remember it was at the axon hillock that it kind of is decided. So the overall positive and negativeness, do we get to minus 55 at the axon hillock? If we do, it triggers an action potential. If we don't, it doesn't. Making sense? So you can see why we now have multiple messages coming in. It's never as simple as it seemed to be at school, is it? Some drugs are able to mimic neurotransmitters, so to stimulate what the neurotransmitter would normally do. Some drugs are there to block the neurotransmitters or to block the receptor. So, for example, beta blockers. These block the adrenaline receptor. So what do you think the effect of blocking the adrenaline receptor would be? Think back to what adrenaline did as a neurotransmitter or as a hormone. It causes flight and fight. So if we block that effect, it's going to calm us down a bit. Hopefully, less of those sympathetic nervous system actions. We'll talk about those in a couple of weeks' time. What about alcohol? Alcohol enhances the effect of GABA. So it enhances what GABA does. Think back to what GABA does. GABA caused chloride channels to open, making it more negative. It was an inhibitory neurotransmitter. So what alcohol does is it stimulates that inhibitory action. What's the effect of inhibiting our nervous system? We become uncoordinated. We become very slow at deciding and making decisions. So it's inhibiting our nervous system. SSRIs, so selective serotonin reuptake inhibitors, these are a type of drug which are there to prevent the serotonin from being cleared from the synapse. Remember I said about how the neurotransmitters get removed or degraded really quickly. What these drugs do is they prevent it from being cleared. It maintains the level of serotonin in the synapse. Can you remember what serotonin was for? It's our happy one, yeah? It's our one that boosts our mood, makes us feel happier. So if we can keep the levels of serotonin higher in the synapse, hopefully we feel a bit happier. So it's often used as the type of antidepressant, SSRIs. I can never pronounce this one, methyl, also known as Ritalin. So Ritalin is a noradrenaline reuptake inhibitor and also a dopamine reuptake inhibitor. Can you remember what noradrenaline was for? So adrenaline was our flight and fight. Noradrenaline was concentration and alertness. So if we can prevent noradrenaline from being cleared, if we can boost noradrenaline in our synapse, it should boost our concentration. It should boost our ability to stay focused. So some people, people perhaps with ADHD, they sometimes benefit from drugs like Ritalin. It helps them with their concentration. It not only targets noradrenaline, though, it's also acting on dopamine reuptake. Do you remember what dopamine was for? It was all about reward, wasn't it? Motivation, making us want to do things more. So if we can boost our dopamine levels, again, it helps us with focusing on our studies or tasks that we need to do because we get more reward from doing it. So you can see that many, many drugs target the nervous system and a lot of them do so by targeting neurotransmitters, either boosting their effect or by blocking their effect. OK, some recap. We haven't done many questions tonight, have we, at all? Oh, terrible. OK, which neurotransmitter has a role in alertness? Which one's for alertness? Adrenaline is one of them, but also noradrenaline. They're related. It's a very overlapping, absolutely. Motivation, dopamine, happiness, serotonin, skeletal smooth and cardiac muscle action, acetylcholine, calming the brain, GABA, cognition, memory and learning. My brains glutinate that one. Because it's not good when the learning and the memory one is the one you forget, that's bad, isn't it? OK. One little bit of about four slides and then I will call it a day for tonight and we will carry on with this next week. OK, I did wonder if we'd get through it all and we clearly haven't. OK, so pulling it all together, we've learnt about action potentials, we've learnt about chemical synapses. So let's pull it all together. Pre-initiation at the synapse. Neurotransmitters such as acetylcholine binds to the receptor opening a channel. Or perhaps sensation, a mechanoreceptor opens the channel. If sodium floods inwards, it's going to make the inside the neuron more positive. In other words, excitatory. If it's opened a chloride channel, it's going to be more negative, inhibitory. We get an overall summation of that input and that will either trigger an action potential or not. If we get to minus 55, it will trigger the action potential. If we don't, it won't. So if it gets a little bit more negative, it opens more of these voltage-gated channels. Let's a bit more sodium in. That opens more voltage-gated channels. Let's a bit more sodium in. That opens even more. If we get to minus 55, it opens all the channels. We get depolarization. We go all the way to plus 40 or plus 61. If we don't reach the threshold, nothing happens and the action potential just fizzles out. All or nothing to trigger that wave of depolarization. We then have those slowly opening potassium channels. They were triggered by the same voltage change as the sodium ones. So sodium ones open fast, but potassium ones are opening a bit more slowly. They're fully open by the time we get to the maximum action potential. So now potassium starts to flow out of the neuron, making it more negative on the inside. We've got repolarization. Potassium channels are also slow to close. They were slow to open. They're slow to close. So we get an overshoot into the refractory period. In the refractory period, it's even more negative than at rest. So in order to trigger the next action potential, you'd have to have a strong stimulus. It would have to be really loud or really hard to stimulate another action potential. So we can't trigger another action potential easily. And so we're back to baseline, sodium potassium pump. But if we get a strong stimulus, we can trigger the next one. Remember, it's always about coding. So we've got jumping down the nodes. Coding is the frequency. It's not the size of the action potential. They're all the same size, but it's how frequent they are. Are they slow or are they quickly firing? That's what encodes the information. Let's leave those for another time. I think we'll call it there for tonight, guys. So we will carry on with the rest of this next week and Anatomy of the Central Nervous System. So we've moved onto the nervous system and we started with neurophysiology.

So we've got as far as slide 55. So now we're going to go back to slide 55. This is from last week's PowerPoints. If you're looking at that board you want to go back to last week and we need to flick right through.

We've always through the structure of the neurons.

We looked at how the cell body of the neuron forms the mind machine producing fatty mind, produces the white matter of the nervous system.

We looked at how nervous messages are transmitted, both electrically through action potentials and chemically through the synapse.

There's still quite a bit of chatter going on. So we looked at electrical conduction, we looked at helical conduction. So our action potential, a wave of positive charge being moved from the outside to the inside as a wave down the length of the axon, triggering the opening of voltage-gated sodium channels and allowing the sodium to move down its concentration gradient flooding into the neuron and then potassium channels opening, potassium flows down its gradient to go outside and that repolarizes our eye neuron. We looked at some equations in the Nernst equation. We looked at how it's all or nothing.

We took some nerve fiber didn't we and how both the diameter of our nerve fibers affects the speed of conduction.

So the bigger the diameter, here we've got the widest ones are fiber 8 alphas, they're 15 micrometers wide, they conduct at 100 meters per second, whereas our smaller diameter fibers, the ones which are really small and 1 micrometer wide, much, much slower and also lamination affects the speed of conduction. We're going to come back to that later.

We looked at coding of neural messages, so remember it's not a size of the action potential, it's not exactly the same size, so it's the frequency that codes the strength of the sensation. So here a moderate stimulus causes a moderate frequency, a stronger stimulus causes a much higher frequency, more back-to-back action potentials. We then looked at chemical conduction, so across the synapse, and how there are different types of neurotransmitter, some of them triggering excitatory signals, those are the ones that open sodium channels. So here we've got acetylcholine opening a sodium channel, when sodium floods inside and it becomes more positive inside, that triggers the action potential. On the other hand, other neurotransmitters opening chloride channels, for example here GABA, GABA is opening a chloride channel where there's chloride negative ions flooding inside, making it more negative, so that calms the nervous system.

So we have excitatory ones, inhibitory ones, and how they body of one neuron, and then it's the summation. So summation is the total input of both positive and negative, what's the overall charge, and whether that reaches that threshold to trigger the next action potential. We looked at how some drugs work, putting it together, we put it all together, and this is pretty much where we got to.

So last week we looked at neurons, individual nerves cells. This week we're going to start looking at nerves, so nerves rather than neurons. So nerves are bundles of neurons found in the peripheral nervous system. So we can see in the picture here we've got lots of axons, so axons are all, each one is wrapped in an endonurium, and they're bundled together and wrapped up in a perineurium, and if we bundle those bundles together, that forms a nerve.

So a nerve is bundles of neurons, and we call those bundles of neurons nerves in the peripheral nervous system.

When we get those bundles of neurons in the central nervous system, we call them tracts, and later today we're going to start those from the nervous system. It's one of its most facts, but for now the nerves bundles of neurons. An example of a nerve would be a sciatic nerve. Now the sciatic nerve is our thickest nerve in the body, it's the diameter of your thumb. That would be your thumb, the thickness of your thumb, that's how big that nerve is in your body, and it runs from the lower back going down the back of the leg.

Okay, so it's tens of thousands of axons, so tens of thousands of neurons bundled together going from the spine down to the other.

We saw this slide, well this picture at the beginning of last week, it summarizes the nervous system. So we had our central nervous system as the brain and spinal cord, and the peripheral nervous system as the nerves coming off of that, and when we look at the kind of flow chart here, we've got in the peripheral nervous system, we've got both sensory, shown in pinky red, and motor, shown in the blue over here.

So sensory nerves are also known as afferent nerves.

Afferent begins with A, so I always think of arriving at A.

It arrives to the sensations from both outside the body and also from inside the body.

Our motor nerves, these are the ones which are triggering muscles to do things, so these are afferent nerves.

Afferent, I think of as exiting, so E for exit, E for efferent. So it exits the central nervous system and it goes out to the body.

So we've got afferent and efferent nerves. So some of the nerves in our body carry sensation, some of the nerves in our body carry motor, and many of the nerves carry both. They have a mixture of neurons or axons that carry sensation and motor. So sensation and one neuron go one way and the motor going the other way in a different neuron. Remember it's bundles of neurons. We're going to start working the sensory ones then.

Sensory or afferent nerves contain sensory neurons and these have specialized receptors that can respond to different stimuli and carry that information typically to a spinal cord and then on to the brain. We're also going to be involved in reflex arcs and we'll look at reflexes at the very end of time. There are different types of sensation.

So we have what's called general somatic sensation. Somatic means on the body. So somatic means on the body and that's in comparison to psyche.

So it means on the mind, so psychiatric for example, psychology means all refer to off the mind whereas somatic is off the body.

So general bodily sensations, things like touch, temperature and pain.

We also have special somatic sensation.

So this is a specialized type of bodily sensation known as proprioception. We'll come back to that in a minute.

We have autonomic sensation.

Now autonomic nervous system is involved in our wrists and digests and our flight and fight. It's sensing what's happening with our viscera.

So our autonomic afferent sensation is carrying messages perhaps from the gut. It might carry messages from the heart but it brings messages into the central nervous system.

Special senses, so sight, hearing, balance, smell and taste. So there are lots of different types of sensation and all of them have different types of specialized receptors. Let's start with our somatic sensation.

Remember somatic means of the body. So this type of sensation is usually referred to as somatic but sometimes it's called cutaneous sensation.

It's sometimes called common sensation or common senses. So here's a picture of some skin. So we've got our epidermis and the dermis and you can see the nerve endings coming through into the dermis. So this is a sensory neuron and it's going to carry that sensation from the body, from the skin, up the sensory neuron, to the spinal cord and then on up to the brain. And it carries messages by touch, temperature and pain. But there's more than one type of touch isn't there? So have a go at this. We've got a night touch, gently stroke your arm. Okay so that's a night touch. But then we've got a coarse touch so we can go for a broad contact. That's actually carried by different receptor endings, the sensor.

There's pressure so we can have quite a deep pressure sensation and then there's vibration. These are all types of touch but they're actually carried in different ways. Temperature, we can detect warm, we can detect cool.

But if we go outside of that, we're going to very hot and very cold. The body just interprets that as pain.

So very hot so we can think of it as a pain message. Very cold is also a pain message.

Most of our temperature is going from cool to warm. Cool to warm.

But again if you had a hot day outside, if you had a mitraloid or the crows in our eyes and we touch the eyes to our arm, we'd feel that as cool. If we stand with the stand we can feel the warmth.

So we can feel temperature. Pain is an interesting one. There are different types of pain. The main one that's a big part at the moment is nociceptive pain. Nociceptive.

Nociceptive pain is what's stimulated by inherited tissues. So things like inflammation, mechanical damage, chemical burning, these sorts of things. These cause nociceptive pain.

The other type of pain is called neuropathic pain. Neuropathic pain is caused by damage to the nerves themselves.

So nerve pain is really horrible, really really painful. You all can cut yourself. That's nociceptive pain.

Some of you have had neuropathic pain.

So some of you have had toothache. Toothache is an example of neuropathic pain.

It's called shingles.

If you've got a trapped nerve in your back or your neck, these can cause nerve pain.

So because they're different types of pain, the medications used to treat them are different. So different painkillers target different types of pain. In order to carry sensation from the skin to the brain, we have a pathway that consists of three neurons.

So three neurons in a row, so remember we have synapses between each neuron.

There's three of them to go from the skin up to the brain. And we're going to look at each of these. We've got a primary neuron, a secondary sensory neuron, and a tertiary sensory neuron.

We're going to start our signal down here in this cartoon up to the right here. This is our bit of skin with a sensory receptor in the skin there.

So we might be rubbing the skin. That initial sensation then is going to be carried by the primary sensory neuron from the skin all the way to where it synapses with the secondary sensory neuron.

The primary sensory neuron then, so this is a somatic sensory receptor in the skin, the axon travels from wherever it is.

It might be in the big toe, it might be in your knee, it might be your arm. That axon is going to travel to the spinal cord. So to the spinal cord where that nerve joins the spinal cord.

It's going to go into the spinal cord at the back. It goes in the posterior side of the spinal cord, and then travels up the spinal cord.

The cell body, remember each neuron has a cell body and axons. The cell body is found, they're all found in little clusters called posterior rhodic ganglions, or dorsal rhodic ganglions. So that's how near the spine little clusters of cell bodies. These primary sensory neurons, because they start in the skin, even though they go up the spinal cord, because they start in the skin, these are part of the peripheral nervous system, the peripheral nervous system.

Once we then synapse with the next one, with the secondary one, this one is now part of the central nervous system.

So our secondary sensory neurons go from where it synapses up to the next synapse. This is our secondary sensory neuron.

This is now part of the central nervous system.

So what we can see here is that the example in the picture here, the primary one, comes in the spinal cord and travels up the spinal cord until it gets to the medulla.

The medulla is part of your brain stem, okay, part of the brain stem. We've got in the picture here, we've got a synapse at the medulla, and then what we get is what's called decarceration.

Decarceration is where the neurons cross sides, so they go from one side of the body to the other side of the body. And that, in this example, is happening at the medulla.

Sometimes that decarceration, that crossing over, happens when the neuron comes into the spinal cord.

So sometimes it comes into the spinal cord and crosses over immediately, and then goes up the other side of the spinal cord.

Sometimes it comes into the spinal cord, goes up its tract to the medulla, and then crosses over. So decarceration, crossing over. The reason our neurons as humans and mammals are that all vertebrates cross over is because there was an evolutionary change when we went from invertebrates to vertebrates, and the evolutionary changes that pass the body rotated 180 degrees. So our bodies used to be with our heads facing that one.

So our bodies are rotated 180 degrees, and now we've got all our nerves crossed over in our medulla, or many in the medulla, okay.

So primary neuron comes from the skin, in at the back of the spinal cord, up the spinal cord until its synapse is in the medulla. The secondary sensory neuron, which is now central nervous system, decussates in the medulla and travels up to the thalamus.

Now the thalamus is a part of the brain that all sensation goes to. Whether that's touch, temperature, pain, hearing, all under-present, they all go through the thalamus. pH, body temperature, pressure, baroreceptors, all those sensations go in via the thalamus. In the thalamus, we then get another synapse. So we've got another synapse to our tertiary neuron, our tertiary neuron.

So again, this is happening in the brain, it's part of the central nervous system. The tertiary neuron goes from the thalamus and it ends up going to the somatosensory cortex. We're going to look at this later. The somatosensory cortex is a strip of brain where we can map where in the body we felt things. That will make more sense later on. In case it's going to a strip of brain, the somatosensory cortex. So three neurons, primary, secondary and tertiary neurons. And notice how if we've got the sensation on one side, it maps onto the brain on the other side because it crosses over or decussates at the medulla.

So the right cerebral cortex is feeling what's happening in my left fingers and my left cerebral cortex is feeling what's happening in my right fingers. Have you all heard of the fact that if someone has a stroke, the symptoms are on the opposite side to where they're happening. This is why. So it's the same idea because the sensations have crossed over. So that's our sensory pathway for our somatic sensation carrying, touch, temperature, pain from our big toe or from our fingers or from our elbow, from our tummy, all the way up to the right. Our next type of sensation is our special somatic sensation, which is known as prop reception.

reception. Prop reception is our ability to know where our body is in space. And this is important for maintaining our posture so I know what my posture is doing. If I didn't know where my body was, I'd probably be walking around like this somehow. It's also important for balance, it's why I can stand on one leg. Okay, so let's test out prop reception. In a program I used to do it as part of the test for some righteous disorder, alcohol consumption, so they would get people to stand on the roadside, either on one foot or one foot in front of the other, close your eye and then can you touch your fingers to your nose. It's not a very reliable test for whether someone's been drinking, but it was better than nothing before the date of regular life. So without hitting your people next to you, first try, point your finger, can you touch your nose. So close your eyes, touch your nose, take your finger away, don't poke it over, can you touch your nose?

Very easy, yeah? Now take your little finger, can you touch your inner? Can you touch the corner of your mouth?

Okay, so to tell of you, easy as can be, but for some people it's a little bit harder. You can only touch the corner of your mouth when you're out of close, if your body can map through prop reception where your finger is and where your lip is, okay?

and where your lip is, okay? So this is prop reception. To work this out, I'm going to have various different senses that are measuring the tension through our tissues to know whether our potential will change if I'm slumped.

The tension changes compared to if I'm upright. The tension in my hand when it's here is different from the tension down here. So this is how my body can tell where bits of me are. So this involves muscle spindles. The senses found in a muscle's tendons and ligaments are called muscle spindles. Here's a picture of a muscle spindle. We're going to come back to this picture later because muscle spindles are also involved in reflexes.

You know when someone goes for a reflex. These are the same senses. So the same senses involved in reflexes are also involved in knowing where your body is, whether my hand is there or whether my hand is there. I know it's strange.

For those of you who have intact sensation, it's hard to imagine that some people cannot tell if their fingers are straight or bent.

or bent. They cannot feel the difference. To those of us who have that sensation, it's hard to imagine not being able to tell the difference. What causes phantom pain?

What causes phantom pain? Phantom pain is a tricky one. So that would be going not through prospective messages, but through it's a type of neuropathic pain. When someone has, for example, an amputation, the endings of the nerves have all been damaged and they try to prepare but they get because of the right tinsules. So they start sending messages up that are not right and that's horrible pain. Again it's a neuropathic pain, not muscle-ceptive pain. So things like phantom pain is not going to respond to paracetamol. Parasympo is great for muscle-ceptive pain, no good.

For neuropathic pain, either open or anti-explanatory.

Great for an inflammatory type of pain, no good. If your nerve endings are tumbling, you need a drug that targets nerve pain like codeine, morphine, you can't be drunk.

Okay, so somatic sensation, our ability to know where our bodies are.

Autonomic sensation. Our autonomic nervous system not only can send out messages to say don't dress or to tell the heart to beat faster or to tell the airways to open up, it also carries incoming messages.

For example, it's part of our sanitation for hunger, for thirst, sickness, nausea, sexual sensation, fullness of your rectum or your bladder. These are all messages that have got to be sent up to your brain.

We saw reflexes, like we saw the reflexes for our somatic system.

We also have reflexes autonomically, for example cough. If something goes down into your airways, it gives a reflex cough.

Our blood pressure, if your blood pressure goes too high, hopefully the reflexes kick in to reduce it. If your blood pressure goes too low, we get vessels present to try and run your blood pressure up. Respiration.

Think back to your age and whether we have a higher load of pH tells us whether to breathe more or to breathe less. Visceral pain is another type of pain.

Visceral pain came from your tummy, tummy ache. Okay, when we have the intestines, if we open someone up and we surf our scalpel through the heart, there are no pain receptors on the small intestine like there are on the skin. It doesn't have the same type of pain detection.

So you can stick an eye for this, not on them. But it does hurt from either ischemia, inflammation, over contraction or over distension.

or over distension. So what is ischemia? What does ischemia mean?

What does ischemia mean? Lack of blood flow and lack of blood flow will cause a lack of oxygen. So we feel this as a visceral type of pain.

For example angina or a heart attack. Someone has a heart attack or angina, we reduce the blood flow to the heart muscle. It causes pain, but it's not the same type of pain as a pain cut or the same type of pain as someone who has a visceral type of pain.

It feels a bit different. Inflammation, that causes pain.

Tonsilitis, you've all felt that. Now that's a mixture of not just visceral pain but somatic pain on the surface of the tonsils. So that's a bit more like kidney pain. But appendicitis, that's inflammation, that causes pain.

But it's a different type of pain to study at home.

Over contraction, over distension.

Those of you who have had tight raps, so your gastroenteritis, food poisoning, and your stomach has gone into spasms and cramps. That's painful. Think about newborn babies having colic. Colic is when the gut goes into spasm and it hurts.

If any of you have ever trapped within the deadlock, it really hurts. Over distension, babies with a trapped fart, but they just can't let go. It really hurts. So visceral pain is no real, but it's carried through different nerves.

30 seconds, you can rest and then we'll go into the motor. So right, so other examples of visceral pain, at some point, that's a visceral type of pain. So caused by contraction, maybe a bit of ischemia going on there as well.

A stitch, those you can go around there. A stitch is when your diaphragm is going into a bit of spasm or an ischemia, not enough blood flow to either the gut or to the motor.

So they originate in the brain and spinal cord and then the autonomic ganglia. We'll look at autonomic nerves next week and we can divide these into somatic, so bodily ones or autonomic.

So the bodily ones are our skeletal muscle contraction.

Contraction, our skeletal muscles can either be voluntary, I can choose, or it can be reflex where I have no choice. For motor neurons, we have two neurons.

I'll show you the picture in a minute. Remember the sensation there were three neurons carrying the message? For motor, it's two. I'll show you the picture next. So these are called upper motor neurons and lower motor neurons.

The autonomic and reverse, these can either be going to cardiac muscle or they can be going to the smooth muscle of the gut or smooth muscle of the respiratory system or they can be going to glands, tearing the bones to secrete or not to separate. Now a lot of these autonomic systems don't actually need neural input.

For example, the heart has its own inbuilt ability to beat but the autonomic nervous system can either speed it up or slow it down, but it doesn't need the nervous system. So the glands, these could be either sympathetic or parasympathetic. They're a bit autonomic, efferent nerves are a bit weird because we have two lower motor neurons instead of an upper and a lower.

It will become a bit more clear later. So here's our motor neurons.

They have this time it originates in the brain. It's going to come down the spinal cord and synapse and then here its synapse is out to the muscle.

The muscle it wants to contract. So we've got an upper motor neuron, part of the central nervous system and we've got a lower motor neuron, part of the peripheral nervous system. So our upper motor neuron here at the top round blob represents our cell body of our neuron. Cell bodies remember gray matter.

So we get a layer of gray matter around the cerebral cortex because of all these cell bodies in them.

Okay so cell body in the motor cortex. The motor cortex is another strip across the top of the head that tells the different parts of the body to move. We'll look at that later.

So from our cell body the axons come through the white matter because axons are fatty so therefore it's white matter and look lo and behold it decussates in the it then travels down the spinal cord so that's going to be going in a tract. Bundles of axons in the central nervous system are tracts.

Bundles of axons in the peripheral nervous system are nerves. So we've got tracts going down our spinal cord and then it's going to synapse at the appropriate level. So if it's going out to a nerve in the arms it's going to go down to the muscle in the leg it's going to synapse somewhere in the lower back.

From that synapse we then have our lower motor neuron.

Notice that's coming out of the front of the spinal cord so it exits the spinal cord from the front sensation went in at the back. Motor goes out at the front.

Our bundles of axons are called nerves and they're going to our end muscle whatever muscle it's going to and that ends at our neuromuscular junction.

So the neuromuscular junction is what your practical is all about. So in the practical you're going to be doing some microscopy and you're and that means that the right side of my brain controls movement on my left and my left side of my brain controls the movement on my right.

So if I have a stroke and I get damage to part of my brain on the left it might cause paralysis on the right.

If it has stroke that causes damage on the right of the brain I will have problems with the motor on the left. Can you have like a better side? A better side. Absolutely we'll have a longer side. Yeah most of us will be done. I don't know what age other than me that left and right kicks in whether children would be naturally ambidextrous but we train them to be one or the other or if they have in their only brain today. I don't know that's a really interesting thought. It also happens in dogs. Doesn't it? Left and right I'm doing this in dogs. I love facts like that.

That's really interesting. Okay so the neuromuscular junction you're going to be listening to the practical and Dr Sam talks about this in the muscle lectures so you get to hear it twice. Okay you heard it once from Dr Sam you hear it once from me and your practical owner. So the neuromuscular junction is the synapse between the nerve ending of the muscle. So rather than nerve to nerve conducting messages is the nerve nerve to muscle and it's going to deliver that message that says contract.

So the motor membrane is the area of membrane across from the synaptic cleft.

So here's a nerve coming in and here's our end plate the area across from that synapse there.

Here we can see one neuron one motor neuron can divide and send out enter that to multiple muscle fibers.

So you might have a motor neuron going to in this picture three muscle fibers or it could go to 1500 muscle fibers and that will change how powerful the contraction becomes because it's telling three fibers to contract or is it telling a thousand fibers to contract.

That will change how strong that is. So at the kind of molecular level just like with our nerve conduction where we had acetylcholine crossing the synapse binding to its receptor and opening sodium channels exactly the same happens.

Here's our nerve ending it's releasing vesicles synaptic vesicles containing acetylcholine they bind to the acetylcholine receptor which opens sodium channels.

Sodium floods into not a nerve because we're not in a nerve anymore it's learned into our muscle cell our myocyte making it more positive inside the muscle cell for a good depolarization just like our axon but it's a muscle.

That wave of depolarization spreads along the surface of the muscle and then down these things called T tubules.

So the wave of positive ions goes along and down that way it can get right into the myocyte right into the muscle cell.

On either side of the T tubules these tunnels going inside we've got the sarcoplasmic reticulum you learned that endoplasmic reticulum in other modules.

Sarcoplasmic reticulum is just like that but it's in muscles. Sarco means muscle a bit so sarcoplasmic reticulum and it contains loads of calcium when that wave of positive ions comes down it opens the calcium channels releasing the calcium from their stores in sarcoplasmic reticulum into the cytoplasm. The calcium that's released combined to troponin C and that then triggers our sliding gland area exposes the sites that the myosin can bind back in power stroke released by power stroke it will do that for as long as the calcium is present and the calcium will be released as long as acetylcholine is present.

So acetylcholine strength is an enzyme that will break down acetylcholine so it removes that initial trigger we stop getting the signals the calcium will go back into the sarcoplasmic reticulum and we stop contracting the muscle. A motor unit a single motor unit is the motor nerve or motor neuron and all the fibers that attaches to. But one motor neuron could attach to 1500 muscle fibers and that's what happens in our big muscles like up quads. One axon comes around and goes to 1500 fibers. Sometimes though it goes to only three so it gives us a much finer control. Each muscle fiber is simulated by only one synaptic butyl so that's one nerve terminal one nerve ending that releases acetylcholine but each motor nerve can go to lots of muscle fibers. So one nerve or one neuron going to in this case we've got quite a few different muscle fibers and it causes all of them to contract. So if the message comes down that axon it will tell all of the muscle fibers it touches to contract. It can't just have some of them and not others it will tell all the fibers that are attached to that neuron to contract. So each motor units each neuron plus the fibers that it's attached to will contract at full capacity.

The strength of the contraction depends on the number of motor units activated. So you've got one motor unit going to five fibers there, one motor neuron going to five fibers there, one motor neuron going to five fibers there. For a strong contraction we want all three to contract, all three to signal, all of those fibers to contract.

For a weak contraction we can just get two of them going or we can just have one.

Motor control depends upon the number of fibers provided by that single neuron.

So to my quads I need lots of power but I don't need fine control. I don't need to be able to write with a pencil with my thighs.

I'm getting it weird but I need fine motor control to my fingers.

So to my finger muscles I'll have one neuron, motor neuron going to just a few muscle fibers. In my quads one neuron going to loads of fibers.

Making sense? Various drugs chemicals can act at the neuromuscular junction to cause paralysis and these can be used in anesthetics, poisons like curate and botox.

Have I got anything written about botox? Botox blocks the vesicle release in the presynaptic neuron.

So how botox works is it stops the release of the astral choline at the neuromuscular junction. If you can't release the astral choline across the neuromuscular junction you can't contract and that then means you can't raise your eyebrows. Okay mixed nerves then.

So as I said in the spinal cord we tend to see the sensation and the motor carry in different tracks.

So you have the bundles of axons for sensation and bundles of axons for the motor in the spinal cord separately.

In the peripheral nervous system we actually tend to mix them all together.

So the sciatic nerve going from my lower back through our bottom down my leg that besides my thumb 10 000 axons in there some of them are motor some of them are sensation. So if I squash my sciatic nerve it's going to give me symptoms of both problems with sensation and problems with motor because it's a mixed nerve.

Okay so if we get impingement or squashing of a nerve it can cause sensory symptoms like pain or pins and needles. Here is a picture of our elbow and this nerve running down the back of the arm and past the elbow here this is our ulnar nerve. I'm sure many of you have whacked your elbow and ended up with pins and needles in your hand yeah we've all done that before at some point. So that was an impingement to a peripheral nerve and it trained the sensory bit of it. So we've got pain and we've got pins and needles. But there's also a motor part as well to these peripheral nerves and that if we affect the motor fibers the motor neurons that will cause weakness and atrophy actually means shrinking muscles where the muscles shrink and get smaller.

If we don't send messages to muscles they will naturally just get smaller they waste away.

So this is our picture of our elbow where we most of us have hit our funny bone at some time we're just whacking the ulnar nerve sending pins and needles down the nerve.

Sometimes though we might have something like a slipped disc where we pinch or trap one of the nerves coming out of the lower back and these nerves go down the leg so that might cause pain coming down the leg it might cause pain in the needles it might cause weakness seeing you're holding on it it could cause the muscles to shrink so atrophy. So that's nerve injuries.

We looked at this one last week why is it that we put our foot in a hot bath so we can feel the bottom before we feel the heat and we know it's all about diameter of our nerve fiber or our neuron and whether it's myelinated or not.

So motor neurons are the fattest and myelinated so they go fast.

Motor neurons conduct fast. Skin touch is the second fastest.

Motor to muscle spindles don't worry about those fast pains this is our sharp burning neuropathic pain and skin temperature are the next fastest and then lower down we have slow pain dull achy pain and we can make the most of this with derivative treatments for pain.

So if you've got a dull achy pain if we can send any of these other messages they will top trumpet they will carry the message faster. So what we can do if we have a booboo we've hurt ourselves here it's sending pain messages nociceptive pain slow pain all the way to the spinal cord it's then going to go up the spinal cord to the brain where it gets mapped onto the brain where you felt that pain but if we can send any of those faster messages we can block that slow pain.

So faster messages anything faster than slow pain will work.

So a change in temperature, skin touch or motor sensation.

So if we've got a booboo what's our automatic thing you value yourself to rub it better it works that's proper science okay that rubbing it out of the skin touch is carrying a faster message to the brain than the slow pain message so we blocked the slow pain. So the suck touch Meccano receptors touch receptors rubbing that same area carries the message to the spinal cord and it will get there faster.

So the message that goes to the brain is the rubbing not the booboo pain not the pain pain.

Neuropathic pain ain't gonna work so well okay this works from our slow pain we can top trump slow pain with skin touch we can top trumpet with temperature so another way you can do it instead of rubbing it better is we can put heat or we can put ice on the booboo that hurts that works what determines which one you use personal reference or whether you think in terms of heat or ice yeah yeah it depends on what you think is going on there's a lot of controversy about this at the moment if it's a chronic pain you might have a level of ischemia so heat will open up your blood vessels producing ischemia but if you've got inflammation and you open up your blood vessels you might think it works ice on the other hand will cause vasoconstriction that can help calm down inflammation but it can also then cause ischemia so the general point of finding to have is you don't your eye doesn't and repeat so it's 10 minutes of ice it's not direct ice it's it's ice density towel 10 minutes on 10 minutes off 10 minutes off 10 minutes off hot water bottles i know you hope you've done anything you just don't want to let go you have to set a timer on that 10 minutes you must take it off 10 minutes off i'll go back again the other example of this kind of working as well as rub it better or ice is a tens machine tens machines you put electrical pads on and it sends the messages faster than the pain messages so again really better ways of just blocking the messages getting up to the right for neuropathic pain there's limited benefits from any of these tens is not bad actually it's not too bad but it's not going to be great okay theoretically the best way to reduce it to block it would be in the fastest ones the lotus so sometimes when people have a page they're going for more it gets better it feels better because they've got the voter sensation go by so you can use anything