neuro

The Nervous System 

  • Divided in two parts: peripheral and central (brain and spinal cord)

  • Peripheral part

    • Divide into autonomic part and somatic part

      • autonomic functions (controls actions of internal organs)

        • Divided into parasympathetic (calming) and sympathetic (arousing)

        • “Fight or flight” 

      • Somatic functions (voluntary and intentional movement)

2 main cell types of nervous system

  • Neurons: main functional unit; involved in sensing external and internal environment, constantly relays information to other neurons that later help modulate behavior of organism 

  • Glia cells: play many different roles such as supporting neurons, helps migration of neuron to their location, help with neuronal communication 

Neurons 3 main things: 

  1. Components of a neuron 

  2. Structure of a neuron 

  3. Classification of neuron 

Classification of neuron 

  • All have a soma (cell body) 

  • Neurons have neurites (axon and dendrite) 

  • Dendrites and axons are in opposite directions. 

  • Axons are extending straight from the soma and not highly branded. Axons send out information

  • dendrites are usually at the end and highly branched. They receive the information because their ends have receptors to have the information

  • Axons and dendrites (neurites) are specific to neurons.  

Nissl stain: 

  •  Can tell you the cytostructure of cells 

  • And can show you the overall morphology of any tissue 

  • Can help to compare the difference between healthy/sick tissue with the density of saw neurons. 

  • Can show you the cell body but can’t give you the complete details of cell 

  • The crystal violet binds to RNA in the neuron

Golgi Stain 

  • Uses a silver chromate stain 

  • Can show the different morphology and can see the individual connections of neurons among different parts of the brain 

  • Gives a better complete picture and can allow you to see entire morphology

Axon 

  • Every axon has an axon hillock (the initial segment that connects the axon to the soma), axon collateral (the branches of the axon), and axon terminal (ends of the axons), and axon proper (the basic long-middle branch of every axon) 

Internal 3 structure of the neuron: 

  • Microtubules: the longest one (20nm); made of multiple strands of a protein called tubulin. Helps transport of cargo by providing tracks for the proteins that need to be moved. “The railroad”

  • Neurofilament aka intermediate filament: middle length one, most abundant of the 3 structures in the neuron helps with mechanical support to the cell. Not involved with cellular motility. 

  • Microfilament: shortest one. Made of protein strands called actin. Hep with cellular locomotion. 

Synaptic communication

  • Synapse is the point of contact between two neurons where transfer of information takes places 

  • Neuron that sends information: presynaptic neuron

  • Neuron that receives information: post synaptic neuron 

  • The space between these two neurons is the synaptic cleft

  • The signal reaches the axon terminal, so now the neruotransmiteers need to get into the synaptic cleft. 

  • Synaptic vesicles has the neurotransmitter and will release them. And they fuse with themembrance of the presynaptic neuron. Then they get release and they bide to the receptors of the post synaptic neuron.  

Classification of Neurons based on morphology

  • Bipolar neurons 

    • Dendrite and axon coming from opposite directions 

    • The dendrites in PNS and axons in CNS 

    • In sensory neurons: the flow of information and location from pns to cns 

  • Unipolar

    • The neurite is splitting into two; one end is dendrite other is axon

    • Dendrite usually found in pns while axon in cns 

    • Also in sensory neurons the flow of information and location from pns to cns 

  • Multipolar: 

    • Both neurites are in cns only OR the dendrites will stay in  cns while axons in pns 

    • Motor neurons: the flow of information and location in from cns to pns 

Classification of Neurons based on neuronal connections

  • Primary sensory neurons: PSN have their neurites under sensory surfaces like the skin and help us sense the external environment 

  • Motor neurons: MNs form connections with muscles and control movement 

  • Interneurons: these neurons only form connections with other neurons. These neurons can relay information between sensory and motor neurons. Only communicating with other neurons. Wont connect to muscles or be located in skin. 

Glia cells: 

  • Broken up into four parts: 

    • Schwann cells

    • Astrocytes

    • Microglia

    • Oligodendrocytes

  • 90% of cells in the brain are glial cells

  • Radio glia cells are a source of neurons so your nervous systems relies on glia cells to divide and reproduce all of the different types of neurons 

  • During embryonic development, radio glial cells can be source for the neurons themselves by generating neurons themselves as well 

Function of Astrocytes: Isolation of the synapse 

  • Astrocytes surround the pre and postsynaptic neurons during synaptic communication 

  • They have proteins that can bind to the neurotransmitters and allow them to be sucked up back into astrocytes

  • This helps regulate neuronal activity and are essential to neuronal survival and loss of astrocytes can lead to neuronal death 

  • They also help with the blood brain barrier with blood vessels in the brain 

  • In the capillaries in the brain, there are no pores/openings contrary to regular capillaries. The “no pore” area is called “tight junction” and they are made by astrocytes since they surround the capillary 

  • This is important from protecting neurons from being exposed to toxins or attacks 

  • Disadvantages are that it makes communication harder between neurons so many drugs are tested to see if they can CROSS that barrier 

Oligodendrocytes and Schwann cells

  • They provide layers that wrap around the axons of neurons 

  • These serve as insulation for the axons which is called myelin and the entire covering is called the myelin sheath

  • Myelin serves to enhance neuronal signaling along the entire length of the axon

  • The difference of these two cells is location. Schwann cells are covering pns neurons in a one-at-a-time rate, while oligodendrocytes are in cns and can myeline multiple neurons 

  • Damage of myelin shows down neuronal signaling/communication 

Microglia

  • The immune cells of the nervous system 

  • Surveys brain for damage or infections and engulf debris and dead cells

Anatomy

Quick Review of Terminology

  • Afferent vs efferent

  • Ipsilateral vs contralateral 

  • Gray matter (cell body) vs white matter (axonal tracks)

    • Gray matter have two categories: nucleus and ganglia 

Nucleus (cell bodies in the cns) vs ganglia (cell bodies in the pns)

Neural Tube Formation

  • Brain and spinal cord arise from a flat sheet of cells 

  • Then it starts to bend in the middle. That bend is called a neural groove

  • As it proceeds the groove deepens which brings the walls of the neural plate closer together which eventually gives rise to cylindrical- like shape that closes at the top

  • This forms the neural tube. The closing at the top is very important. If it fails to close then it can lead to deformities, this can occur usually in the first trimester of pregnancy. 

  • Exposure of certain environmental factors can lead to closer defects like drinking alcohol and taking valproic acid (anti-seizure medication)

Neural Tube

  • There are 4 parts formed by the neural tube which make up the cns 

  • Prosencephalon (forebrain), Mesencephalon (midbrain), and Rhombencephalon (hindbrain), and the spinal cord - posterior part

  • If the neural tube fails to close in the most anterior portion (more severe) = anencephaly

    • lethal

  • If it fails to close in the posterior portion (less severe) = spina bifida 

    • Can be fixed with multiple surgery but will still have urinal, digestive issues

Basic components of cns 

  • Biggest structure is cerebrum

    • Divided into left and right hemispheres

  • Highly folded part is cerebellum 

  • Brain stem is in the back which has importance for autonomic activities 

  • Then you have spinal cord for movement

Growth along three different axes

  • Anterior (head) - posterior (feet)

    • Top to bottom axis 

Major Subdivisions of the CNS

  • Forebrain (most anterior)

    • Telencephalon 

      • What makes the cerebral cortex (folded structure)

        • It is divided into 4 lobes: frontal, parietal, occipital, and temporal

          • The prefrontal cortex is what allows us to do problem solving and it uses information from the sensory motor areas 

        • These folds of the lobes are a characteristics of primates and indicates how many neurons are in the restricted space

        • The folds are called gyrus and the deeper grooves are called fissure and they divide the brain folded into those specific lobes 

        • The central sulcus divides the frontal and parietal lobe 

        • Precentral gyrus (frontal lobe): 

          • motor cortex

            • Contains the motor connections made with neurons 

            • Responsible for sending information to control voluntary movement 

        • Postcentral gyrus (parietal lobe): 

          • somatosensory cortex

            • Receives the sensations felt by the body 

        • Superior temporal gyrus: 

          • auditory cortex

          • In the temporal lobe 

          • Auditory cortex

          • Ability to perceive different sounds 

        • Hippocampus

          • Learning and memory

          • Henry molaison

        • Amygdala

          • emotion

        • Basal ganglia 

        • Olfactory cortex 

    • Diencephalon 

      • Thalamus

        •  Relays information from several sensory inputs to the cerebral cortex

        • One exception is the sense of smell (it does not go through the thalamus but instead straight to cerebral cortex)

      •  Hypothalamus

        • Will have issues with developing memories if hippocampus is destroyed 

        • Henry molaison suffered from severe epileptic seizures so doctors wanted to know what caused it. They removed this part of the temporal lobe and got rid of the seizures. However, it also contained the hippocampus so he later suffered from amnesia and could no longer form new memories (factual memories)

        • But he could still retain the ability to learn new skills and still remembered things from before the surgery

        • This shows us that older memories are not located in hippocampus 

        • Maintains homeostasis (feeding, drinking and thermal regulation)

      • Cingulate gyrus

        • Plays a role in emotional processing 

      • Corpus callosum

        • Connected the right and left hemisphere 

  • Midbrain 

    • Superior colliculus: 

      • receives visual input from the eye

      • Enable us to move head and eye in the object that you would want to see

    • Inferior colliculus

      • Receives auditory input from the ear and would send it to the thalamus

    • Periaqueductal gray matter: 

      • suppression of pain 

      • Help mediate emotional responses (the amygdala sends it neuronal connections to here and help us express our emotions)

    • Substantia Nigra and red nucleus: 

      • Voluntary motor control 

    • Tectum

    • Tegmentum

  • Hindbrain 

    • Pons

      • (a relay center) Contains important axonal tracts that connect the motor cortex to cerebellum

      • Helps regulating sleep cycle

    • Medulla

      • Medullary pyramid

        • Axonal tracts running from the cortex to the spinal cord enable control of voluntary movement

      • Ventral and dorsal cochlear nucleus

        • Important for processing of auditory information 

        • Then sends this information to the inferior colliculus

    • Cerebellum 

      • Cauliflower shaped 

      • finetuning a new motor skill/control (playing an instrument/playing a sport)

      • Drinking alcohol affects it and prevents “precise” movements

      • Both sides of the cerebellum are connected by the vermis 

      • Prevents us from tickling ourselves because our cerebellum can quickly predict the sensations it is about to do so it suppresses the somatosensory neurons

  • Spinal cord

    • All of the sensation you feel are sent to your spinal cord through spinal nerves

    • It is broken up into 4 parts

      • Cavial: head and neck

      • Thoracic: chest and back

      • Lumbar: lower back

      • Sacral: lower parts of body

    • Dorsal horn 

      • Receives information from sensory neurons such as touch, pain, temperature

      • Contain interneurons

    • Intermediate zone

      • Contain interneurons

    • Ventral horn 

      • Controls movement of muscles in response to the sensations received by the dorsal horn

      • Has motorneurons which will send their signals out to the muscles and that controls different sets of muscles in your body


Knowing your way around the CNS: the ventricular system

  • While the walls of the neural tube form the different regions of the CNS, the lumen within the neural tube makes the ventricular system (everything inside the neural tube) 

  • Ventricular system’s job is to secrete cerebrospinal fluid (provide a protective cushion for the brain whenever we fall or get tackled)

  • Note: all ventricular portions are connected for the fluid to pass 

  • The lateral ventricles = telencephalon 

  • Third ventricle = thalamus and hypothalamus 

  • Cerebral aqueduct = tectum and tegmentum 

  • Fourth ventricle = pons, medulla, cerebellum 

  • Spinal canal

Why is studying embryonic development useful

  • Holoprosencephaly

  • Medulloblastoma

  • Pallister-hall syndrome

  • Basal cell carcinoma

Establishing Neuronal Connections

  • Pathway selection-what path will axons take to get to the right structure

  • Target selections- which nuclei will the axons target within the right structure

  • Address selection- which specific class of neurons will the axons form a synaptic connection with within the nucleus 

  • When an axon travels down a specific pathway there are certain molecules that can act as an attraction or repulsion. Ask pandit later

Commissural axon guidance in  the spinal cord 

  • NOTE: the growth cones of each axon needs the specific receptor to sense the matching chemorepulsion or attraction

  • Presence of BMP in the roof plate acts as a chemorepulsion is what prevents the axons to move to the dorsal side of a spinal cord. The receptor for the BMP is the BMPR

  • Then an attractive cue called Netrin located in the floor plate pulls the axons to the ventral side. The receptor for the netrin is DCC

  • Now the axons need to cross over the midline and go to the other side for a contralateral effect. Now another chemorepulsive cue is released called Slit to move the axon across the mid line and there matching receptor is Robo

  • Finally, aftering crossing the midline, the axons need to move from the posterior to the anterior of the spinal cord. There is a signaling chemoattractant molecule called whit and as you go from posterior to anterior the amount of signaling of chemoattractant increases. The matching axon receptor being released is FZ. 

Refining Neuronal Connections

  • Programmed cell death- recording 

  • synaptic pruning 

    • A presynaptic neuron is sending axons out but it will send out multiple axonal branches to establish multiple connections. In some cases not all branches will be used so they will be selectively pruned because it is not being used. This can be done by degraded/pruning or the smaller branches will be retracting/absorbed by the main axonal branch. This makes sure the amount of the connections are decreased and it perfectly matches the target. 

Membrane Potential


Resting Membrane Potential

  • The difference in the electrical charge across the membrane. In the absence of a stimulus, it is at “rest” and at around -65 mV. 

Factors playing a role in generating resting membrane potential of a neuron 

  • The neuronal membrane

  • Proteins embedded within the neuronal membrane

  • Ions inside and outside the neuronal cell 

Neuronal environment 

  • The phospholipid bilayer of neuronal membranes provide a barrier to the entry of different ions present both inside and outside the neuron

  • The neuronal membrane is made up of phospholipid bilayer. The phosphate groups are on the outside and hydrophobic parts are on the inside. 

  • With this barrier being made, in order for certain ions to pass through, there are different proteins to allow certain ions to pass.  

  • Proteins embedded within the neuronal membrane

  • Ion channels

    • Tend to allow ions like potassium to move down their concentration gradient

  • Ion pumps 

    • Tend to move ions against the concentration gradient. Requires energy like ATP.

Different types of IONS

  • K+

    • Potassium 

    • High concentration INSIDE

  • Na+

    • Sodium 

    • High concentration OUTSIDE

  • Ca2+ 

    • Calciu 

    • Very low concentration inside (0.00002) kinda low outside (2)

  • Cl-

    • Chloride

    • High concentration outside 

How we measure measure membrane potential

  • Sea Squid axons were studied and placed in salt water to mimic the normal environment 

  • Two electrodes were placed in the same solution of salt water so there was no charge

  • Then one was kept in the water and one was put in the membrane of the axon of the squid 

  • The difference was -65 mV and it shows how the inside of the axon is negative and more negative compared to the outside 

How do ions move across the membrane 

  • Two types of forces dictate the entry the exit of an ion into the cell through ion channels

  • 1. Diffusion 

    • Ions will move from higher concentration to lower concentration (too crowded needs to more space to breathe)

  • 2. Electrical 

    • There is a charge and that opposite charges will attract and same charges repel

    • This will generate a electrical current

  • There needs to be ion channels and a concentration gradient for ions to move

  • Concentration gradient = unequal amount of type of ion on one side 

  • Force of diffusion = electrical force (this is called equilibrium potential)

  • Positive equilibrium = permeable to Na = 62 mv

  • Negative equilibrium = permeable to K =-80 mv

  • For every 3 sodium ions going in there will be 2 potassium going out

Importance of selectivity in ion channels 

  • At rest without a stimulus, there are channels that are more selective to potassium ions leaving the cell versus sodium ions entering the cells

The importance of regulating extracellular potassium ion concentration 

  • Astrocytes allow the potassium to be equally distributed along the neurons to regulate the concentration in case there is a disturbance.

  • Muscle cells don’t have astrocytes do they have a harder time trying to regulate concentration if they have a disturbance hence irregular heartbeat or muscle tremors


Action Potential


How are action potentials initiated

  • Sensory receptors → sensory neurons → interneuron → signal sent to motor neuron → muscles and spinal cord 

Action Potentials

  • How is the membrane potential changing during an action potential 

  • Resting potential : when it is at rest at -65mv 

  • When it becomes more positive (depolarization) : rising phase 

  • When it goes back down to negative value lower than resting value : hyper polarization : falling phase 

  • Overshoot: 0-40 mv

  • Undershoot: going lower than resting membrane potential  

Ionic permeabilities across neuronal membrane at rest

  • In the absence of a stimulus, a neuron has resting membrane potential and the permeability of the membrane to potassium ions is higher than permeability to sodium ions

  • Rising phase of an action potential

    • Consider an event where permeability of the neuronal membrane is higher for sodium ions than potassium ions

  • Falling phase of an action potential

    • Consider an event where permeability of the neuronal membrane is higher of potassium than sodium

Action potentials- important to note

  • All or non 

  • It will fire an action potential or not 

  • It is how much it will fire 

  • Increasing stimulus intensity = increase in firing rate

  • Absolute refractory period: when a neuron cannot fire another action potential periodt

  • Relative refractory period: when a neuron cannot fire another action potential unless there is an increase in the stimulus

  • How do ion channels contribute to the rising phase of an action potential

  • Sodium can enter the voltage-gated sodium channel through the opening 

  • The channels have selectivity filters that only allow sodium ions to pass through the pores

  • Voltage sensors are a string of charge amino acids residues in the membrane of the channels, if they sense a change in the membrane potential (which is a change in the permeability to sodium ions)  then they are what allow the channels to open 

  • They open at -40mv

  • This first opening of the selectivity filters is when there is a small change in the membrane potential from a stimulus

Opening and closing of sodium channels during an action potential 

  • Opening and closing of sodium channels is not adequate to explain the different places of action potential

  • The closed conformation of the sodium voltage gate channel is the inactive activation, the ball swings inside and it makes it a barrier stopping it from being an higher overshoot

How do ion channels contribute to the falling phase of an action potential

  • Like voltage-gated sodium channels, voltage gated potassium channels also contribute to the action potential

  • The fact that sodium ions can’t enter anymore

  • Now the voltage gated potassium channels open (more slowly than the sodium channels) and the potassium ions will start to the leave the inside and then the membrane potential goes down to -80 because all of the potassium channels are leaving 

  • Once you get to the -80mv, the potassium pumps will start to close again which will allow the membrane potential will go back to -65

What if you could not sense the hot flame of the candle

  • F

Propagation of an action potential 

  • Axons of neurons send information over long distance through action potentials 

Factors affecting propagation of an action potential 

  • Axonal diameter

    • Wider = allow ions to move more efficiently

  • Insulation (myelin)

Myelination and saltatory conduction 

  • The “jumping” of action potentials from one node to the other is called saltatory conduction

  • It prevents any leaking of the ions out of the cell

The effects of toxins on action potential

  • Pufferfish release tetrodotoxin and it prevents the opening of sodium channels which prevents action potentials to generate