Patho briski

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Our discussion. We had defined what a plexus is somewhat incomplete, but I would like to finish that definition right now. You recall that we had set a plexus. And if you look at the illustration here at the left hand side of the slide, we're taking a dorsal view on, first of all, the spinal cord here, and it is divided into regions using the color code, cervical, thoracic, lumbar, sacral, and coccigial. And you'll notice that with the exception of the thoracic region where spinal nerves exit nicely and rather simplistically, in other regions of the body, there is so called, at least visually, what appears to be a tangle.

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Or an enmeshment of nerves. We will define these as a plexus. It's important to keep in mind that the plexus is a branching network that has both sensory and motor fibers or axons. But importantly, what we didn't have a chance to explain on Friday was that we're going to form plexuses using a ventral ramus of a spinal nerve. So to explain what a ventral ramus is, I'm going to ask you to look now at this large illustration in the upper right hand corner. For orientation purposes, this is the dorsum of the body. This is the ventral body wall, lateral body wall here. For

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Orientation purposes, these are two segments or parts of a vertebral bone. Here we're looking at a cross-section through the spinal cord, which we have not viewed as yet. But I want to draw your attention to the structures in this black rectangular box. And I'm going to begin here with this scarred item, namely a spinal nerve. And it can be viewed directly lateral to the confines of the vertebral bone. Almost immediately upon the formation of a spinal nerve, it divides into two important branches, namely a dorsal ramus and a ventral ramus. And we can see these here. This is the.

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Dorsal ramus. This is the ventral ramus. The dorsal ramus is relatively short and smaller or smaller in diameter, and it innervates the so called hepaxial muscles associated with the dorsum of the body. These muscles keep us in extension. The larger ventral ramus longer and we can follow it through here provides innervation to the musculature of the thoracic body wall. So back to our definition of a plexus. A plexus is formed by the exchange of fibers of ventral rami of

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Specific cranial nerves. Down here, we have a sort of an overview explanation of what different plexuses, the structures that they innervate. Importantly, keep in mind, each plexus has a unique set of efferent structures. There's no overlap. Very briefly, we can say that the cervical plexus, indicated here, innervates musculature associated with the head, neck, and shoulders. In contrast, the brachial plexus, nice salmon color here, musculature associated with the chest, shoulders, and upper extremity, arm, forearm, hand.

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By contrast, the lumbar plexus innervates musculature of the back, abdomen, groin, thighs, knees, and calves. Sacral, musculature of the pelvis, the buttocks, the glutei muscles, for example. Muscles associated with the genitals, thighs, calves, and feet. In other words, components of the lower extremity. And finally, the coccygeal plexus, or I would say the coccygeal nerve, innervates musculature in a small area over the coccygeal bone. Now there's several different plexuses which we have given a brief overview to here. On the next slide is a more detailed

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Explanation of the musculature innervated by these various plexuses. I will let you read this. This is kind of like a review or an extension of what I just said. And in addition, just to keep in mind, in addition to somatic plexuses formed from spinal nerves, there are additionally autonomic plexuses. But let's go back to this illustration. I'm not going to talk in detail about each of these specific plexuses, but I'm going to focus on the brachial plexus. And this plexus is formed from ventral rami, apherent and efferent fibers, of spinal nerve

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nerves C5, six, seven, eight, and t one. Again, so a distinct subset of spinal nerves. Their rami contribute and make up the brachial plexus. Now this merging of ventral rami fibers is not a simple let's add some fibers and let's create some nerves. There are, very interestingly, an exchange of fibers over three different levels, or so I would say different levels of exchange. These rami initially form trunks, and I have a better illustration next two slides. So hold on for a minute. And I'm not gonna ask you to memorize these sequential exchanges. I just wanna give you an idea of the complexity and

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Here. So the rami first form trumps, then they go on to form divisions, but they don't stop there. They go on to form cords. And finally, five distinct nerves are generated, namely, and I've used a symbol for several of these because I'm going to later explain the specific muscles of the arm, forearm, or hand that they innervate. We're going to create from the brachial plexus the musculocutaneous, the axillary, the median, the radial, and the ulnar nerves. So this is again

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I'm not gonna ask you to memorize this. Uh, this is the creation from ventral rami of these specific cranial nerves, the formation of roots, trunks, and notice that we're proceeding from through these levels of integration or merging from medial to lateral. Roots, trunks, divisions, cords, and then finally those five specific nerves that we identified on the previous slide. Now, what is the purpose of this particular graphic? It is complicated. Again, I'm not gonna ask you to memorize. I'm only going to concern myself largely-

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With this grouping of information and just very briefly this. But what are we seeing here? We are looking at in total all of the named somatic muscles associated with the attachment of the upper extremity to the trunk and all of the various muscles that move the arm relative to the trunk, the forearm relative to the arm, and finally movement of individual fingers. So here we have, and we're not gonna pay any attention to this grouping, muscles that attach the scapula to the humerus. And, again, I'm not gonna ask you to memorize this, upper limb, upper limb to thorax.

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We're going to start here. The information here in a nice purple color. Musculature associated with the arm. So now we're going to move from medial to lateral. And what is the next piece of information provided? We're going to consider that the arm has muscles on both an anterior and posterior compartment. Why? Because most somatic muscles act are placed in groups that have an antagonistic action. So moving further laterally, we have now the names of individual muscles, for example, in the anterior group, biceps brachii, coro.

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Brachialis and brachialis. Notice they are all innervated by the musculocutaneus. Okay. So what do they do? Contraction of these muscles in the anterior compartment causes a reduction in the the angle between the forearm and the arm. What does the muscle in the opposite antagonistic compartment do, namely the muscle in the posterior or dorsal compartment? That is the triceps located here. Contraction of this that muscle has the opposite effect to increase the angle between the arm and the forearm. It is

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Instead innervated by the radial nerve. So we're learning here a very important concept. All named somatic or voluntary muscles are innervated by a single named nerve. There is no overlap. What this tells us here is that the function of muscles in the anterior compartment can be impaired or inhibited to some degree depending upon a level of damage to the musculocutaneous nerve. In contrast, full functionality of the triceps here requires innervation by the radial nerve. So now let's

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move on to, and we have this example here. Let's go to muscles of the forearm. Notice they're organized by compartment: anterior, lateral, and posterior. What I would like to briefly point out at this time is that muscles here, indicated in a tan color, occupying the anterior compartment of the forearm, are innervated by the median nerve. So this is distinctly different from the innervation of the musculature of the arm. Now, let's talk about musculature-

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In the lateral, in a pink grouped here, and finally in the posterior compartment of the forearm, innervated by radial nerve. Now I have a similar example or set of examples here about the contribution of the bra- lumbar and sacral plexuses to innervation of muscul- musculature of the lower extremity, but I'm not-- I'm going to pass over this material. I'm simply going to focus on the brachial plexus as an example of a complex exchange of fibers, providing named nerves-

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Innervating specific voluntary musculature involved with various levels of the upper extremity. So here we have a similar grouping of musculature depending upon where they're organized on the thigh, the leg, and the foot. And again, the purpose here, I'm not gonna go into this in any detail whatsoever. I'm not gonna ask you to memorize this, is that these groupings of muscles receive specific nonoverlapping innervation. Now I would like to move on to a very classical illustration that has been used by neuroanatomists for probably more than a century. But

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Before we begin, I want to, uh, direct your attention to the upper left-hand corner, and what I have illustrated here for review purposes are cartoons of two neurons. The one on the right here, you'll notice has a polygonal-shaped cell body, a extensive branched dendritic tree, a single axon. This is our class, a representative of our, our class A neuron, a, a multipolar neuron. Okay? To the left of that now instead is a neuron with a cell body that is circular or round, gives rise to a single process that immediately divides into two subbranches. Mm-hmm. One directed peripherally, so-

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serving as a dendrite, the other directed centrally, serving as an axon. We have already said that this, that neurons in this class C are essentially sensory in function and are located in dorsal ganglia or sensory ganglia of spinal nerves. In the next few minutes, I'm going to show you the location of a dorsal root ganglion. So now to the image in the center of the slide. For orientation purposes, this is the dorsum of the body. This is the ventral surface. We're directed toward the ventral surface. We're looking at a cross-section through the spinal.

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Cord here. And as is noticeable with the visible eye, if you take a fresh fresh slice or section through the spinal cord, what is very obvious is that there's a distinct coloration difference between the periphery of the spinal cord versus the central regions. So we divide the components of the spinal cord into white matter, which is external. And we're going to subdivide the white matter into distinct regions called funiculi. Funiculus singular. Faniculi plural.

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Depending upon the orientation toward the dorsal body wall or the ventral body wall. Okay. Opposite there. So this portion of the white matter is the dorsal finiculus. This is the lateral finiculus, and this is approximately the ventral finiculus. The significance of naming these subregions of the white matter will become apparent in the next few minutes. Now internal to the white matter is the so called gray matter here, and it has a distinctive butterfly shape, resembling an expanded H, if you will.

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We're going to divide similarly the gray matter again according to orientation toward the dorsal body wall or the ventral. So we will name this segment of the gray matter as the dorsal horn. That segment oriented in the opposite direction toward the ventral body wall, we will instead call the ventral cord. Now I'm going to direct your attention now to the other side of this illustration in discrete regions.

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Or levels of the spinal cord, not throughout the entire length of the spinal cord. Only in discrete levels, we will find a distinctive lateral horn. Whereas the dorsal and ventral horns exist throughout the entire length of the spinal cord, the lateral horn, again, to repeat myself, is only present at distinct levels, and I will identify those in a few moments. So we've identified now the internal composition or describe the internal composition of the spinal cord. Now let's observe the creation of spinal nerves.

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This is a spinal nerve here. This is a spinal nerve here. What the artist has not indicated on this illustration is that this tiny branch is the dorsal ramus, and this larger branch is actually the ventral ramus. So as I said a few minutes ago, as soon as a spinal nerve is created, in other words, they're relatively short, they immediately divide into a dorsal ramus and a ventral ramus. But how do we create a spinal nerve? Now we're going to use some color coding. I'm going to use a blue to identify a ferrin or sensory fibers.

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And in contrast, I'll use pink to show efferent or motor fibers. I'm going to draw your attention to these two tubular structures that emerge or are directly continuous with the spinal cord. These are called roots. And once again, we're going to name them according to their proximity to the dorsal or ventral body wall. And so we will name this one the dorsal root because we had said this is the dorsal body wall here. And correspondingly, this is the ventral root. When the two roots unite

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They create a spinal nerve. Notice the coloration difference between the dorsal and ventral root. What we're seeing here using blue is to indicate that only sensory or apherent axons or fibers are located in the dorsal root. So the dorsal root, we can say, is the conduit which carries sensory fibers and sensory information into the central nervous system. In contrast, if we look at the ventral root here, it serves as the conduit to

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Carry outward motor or efferent fibers. So another way to look at this or to summarize is sensory information enters, motor information exits the spinal cord via different routes. So now we're going to discuss and you probably noticed from the very beginning that this illustration is halved, but the halves are not identical. This gives us an opportunity to talk about inflow, sensory information, outflow of visceral of efferent information.

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That targets somatic effectors, which is skeletal muscle, versus the collection of visceral effectors, namely smooth cardiac muscle, glands, and adipose tissue. So I'm going to direct your attention to the left hand side of the illustration. We're going to be discussing somatic afar and input, somatic afferent output. So somatic a ferrin information, and this is a little bit of a repeat here, is information provided from receptors in the skin reporting on touch, pressure, pain, thermal insults, etc. There's

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Also information provided from joint proprio receptors and joints. This information is carried up to the dorsal root, and the cell bodies of these sensory neurons are located in a bulge associated with the dorsal root. Every dorsal root in the nervous system contains cell bodies of sensory neurons. Now the axons enter the spinal cord here, and they may they may contact what we call short interneurons, which are having a modulatory effect. Or alternatively, they may synapse with

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A motor or efferent neuron whose cell body is in the ventral horn. And this is an example here. At this point, I'm going to give those motor neurons in the ventral horn a specific name, which I will repeat in the next few minutes. I'm going to call it a lower motor neuron. This is specifically relevant to somatic efferent outflow, not autonomic. That cell body gives rise to a very long axon which enters the ventral root, enters the spinal nerve, can enter either the dorsal ramus or the ventral ramus and run on to directly innervate.

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One or more skeletal muscle fibers. Very long axon. Now let's move to the other side of the illustration, where if you think back to one of the slides I used Friday where we discussed how visceral efferent innervation is a much more complicated affair involving both preganglionic and postganglionic visceral efferent neurons. Correct? Think back to that slide because now we're going to use that information. So.

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Please turn your attention now to the right hand side of this illustration. Here we have a dorsal root and a ventral root, and notice that they contain blue versus pink axons, conveying a ferent versus efferent axons. So visceral efferent information. Information on pH, carbon dioxide, oxide concentrations of tissue fluids, pain, stretch, injury to viscera. This information is carried into the central nervous system by a ferent neurons, and their cell bodies are also located in

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Dorsal root ganglion. Now you can always distinguish a dorsal root from a ventral root because the dorsal root has a ganglion or bulge. The ventral root does not. Oops. So this information is carried into the central nervous system. But now I'm going to turn your attention to that lateral warn. Within the lateral horn are cell bodies of preganglionic visceral efferent neurons. So they're not in the ventral warren where the lower motor neurons or somatic efferent nortons are located. They're they are

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Found in a distinctly different location in the gray matter. So they give rise to axons. They and there are three representative preganglionic neurons. Why? Because they synapse with postganglionic neurons either in a different place or a unique place. And the postganglionic neurons go to three different individual locations. Bear with me, please. So all three of these preganglionic visceral eupherent neurons are going to enter the ventral root, as you would expect. But now we're going to go through each of

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These three distinctive routes. I'm going to use this preganglionic neuron as the first topic. And right now I'm going to introduce two additional structures that are very important. Please look at the spinal nerve here and notice there are two branches or rami directed downward. These are white rama the white ramus and the one more medially is the gray ramus. And notice our representative preganglionic neuron.

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Exits the spinal cord, enters this white ramus, and in a autonomic ganglion located very close to the spinal cord and vertebral column, it makes synaptic contact with a postganglionic neuron. Now color. This is an important piece of illustrative information. Preganglionics here, solid pink. Postganglionics, dotted pink. So now let's see what the postganglionic dotted neuron or axon does. It travels through the gray ramus and reenters the spinal cord.

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This this collection of postganglionic visceral epherent neurons collectively innervate a discrete set of structures. Smooth muscle in blood vessels. Smooth muscles that act to cause extrusion of sweat from sweat glands. And I have another structure here. Okay. Oh, smooth muscle associated with air follicles that makes your hair stand on end. Okay. Now let's look at

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Representative preganglionic neuron here enters the white ramus and stops in that nearby ganglion, gives rise to a postganglionic neuron, which then travels on to visceral efferent effectors. So so far, both of our representative preganglionic visceral efferent neurons have used a local motor ganglion. It has stopped there to synapse, but the postganglionics go off and do different things.

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In the first instance, that postganglionic uses spinal nerves to reach vasculature, erector pilli muscles of hair follicles, and sweat glands. In the second, more recent, example, those postganglionic neurons arising in that local motor ganglion innervate cardiac, smooth muscle, adipose tissue, etc., different targets. Now, finally, our third here once again enters, leaves the spinal nerve through the white ramus. But instead of stopping at one of these local ganglia, this post preganglionic

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travels to a one of three to five distinct ganglia located very close to the ventral body wall. This is another set of autonomic ganglia. Now, let's take a step back, and the postganglionics then travel on to cardiac muscle, smooth muscle, etc. Let's talk about these autonomic or motor ganglia. The first of these, I'm not gonna give a name. I'm gonna call it a vertebral ganglion because they're located very close to the outside of the vertebral column. They're alternatively called paravertebral ganglion. This indicates the close proximity to

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The newly created spinal nerve. The other ganglia, the three to five, the prevertebral pre as a prefix simply means closer to the ventral body wall. Now let's get back to these white and gray rhyme. Why is one white? The more lateral is white, the more medial is gray. And if you look at them in a dissection, they truly do have a different color. The preganglionic visceral efferent neurons are myelinated. Remember, think back to our our chart or table. They're in fiber

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Class B, I believe. Postganglionic visceral eferente neurons, remember I told you those are unmyelinated. So in this case, this dotted postganglionic neuron uses the gray ramus to regain access to the spinal cord and travel to these distinctive structures. So that explains the coloration difference between white and gray ramus. Myelinated axons, unmyelinated axons. Now, interestingly, as I told you, most structures, visceral epherent structures receive dualistic or antagonistic innervation, sympathetic

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Versus parasympathetic. The paravertebral vertebral and the prevertebral ganglia belong exclusively to the sympathetic branch of the autonomic nervous system. Parasympathetic postganglionics are extremely long, and they travel directly in most cases to contact postganglionic neurons within the wall of the visceral structures to be integrated. So now using this histological microscopic basis or foundation of information, we're going to return to the topic of the autonomic nervous system.

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But the information here more or less extends and uses terminology and concepts we have just discussed over the past ten minutes. So here we have on the left hand side sympathetic nervous system. Here on the right, we have parasympathetic. For orientation purposes, we have the brain. It is continuous with the spinal cord in both illustrations. I'm going to direct your attention and notice that there is a numbering according to body region and levels or or specific pairs of spinal nerves that arise from those levels. C one through eight.

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T one through twelve, etcetera. In talking about the sympathetic nervous system, I'm going to draw your attention to levels T one through L2. At those levels, we will observe a lateral cord. At those levels of the spinal cord only, do we have sympathetic preganglionic visceral epherence? Okay? Now to draw your attention to the extreme left of this illustration

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Think back to our first representative preganglionic visceral efferent neuron, where essentially the postganglionic neuron arising from a vertebral ganglion utilizes spinal nerves at every level in the body to innervate this distinctive grouping of structures. This is essentially what is illustrated at this point. So that that is another look at example number one. Example number two.

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There are distinctive preganglionic sympathetic fibers that make synaptic contact within specific components or or specific vertebral slash paravertebral ganglia and give rise to and again, pre and post are solid pink or dotted pink. After synaptic contact in vertebral ganglia, there is postganglionic innervation of a range of important structures.

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Now finally thinking of or referencing our third example where the preganglionic bypasses the vertebral ganglion cluster. That would be inner outflow from these levels and instead makes synaptic contact with either the celiac ganglion, superior mesenteric, inferior mesenteric. Those three structures are the major prevertebral ganglion. So this illustration again extends or builds upon the information we had for the terminology that we had introduced previously.

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This gives us now our first look at the various diverse collection of structures innervated by both sympathetic and parasympathetic. Now we're going to talk about parasympathetic outflow, but all of these structures listed or depicted in the middle of the slide receive again this antagonistic outflow. These structures are unique. They only receive sympathetic information or direction. So functionality of sweat glands.

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Solely under command or control of the sympathetic nervous system. Importantly, vasculature associated smooth muscle associated with blood vessels. Sympathetic control also. And again, to repeat, that information is carried, those sympathetic fibers are carried by spinal nerves. And finally, the erector pilli muscle here, which can raise or lower air follicles, sympathetic control exclusively. So now parasympathetic. Again, all of these structures, visceral entities depicted here receive parasympathetic in addition to sympathetic. So whereas we said in terms of sympathetic

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Outflow, we're looking at T1 down to L2 to look at where the preganglionic neuron cell bodies are located. We're going to look in different regions of the central nervous system now to look at cell bodies that give rise to parasympathetic preganglionic axons. The parasympathetic division is alternatively referred to as the cranial sacral division. And that name is very explanatory or intuitive. And that's because preganglionic neurons are located either in the brain or sacral levels.

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Two, three, and four. For general purposes, we can say that from the level of the brain, parasympathetic preganglionic outflow is carried by four specific cranial nerves. And as we will discuss in the next lecture two or three down the road, cranial nerves are identified either by a given name or a Roman numeral. At this point, I'm not gonna ask you to memorize the given name, but I need for you to remember three, seven, nine, and ten.

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At this point, I'm not going to talk very much about outflow via three, seven, and nine, but I am going to draw your attention to cranial nerve ten. It is also called the vagus nerve. And as we can see here, it provides innervation to a large, incredibly diverse multitude of visceral structures. Now, finally, as I said a minute ago, there is parasympathetic preganglionic outflow from the sacral level of the spinal cord. And in the sacral, those three sacral segments, we will find a lateral port. So again, this

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Reiterates the point that dorsal ventral horns throughout the entire length of the spinal cord, lateral horn only levels T1 through L2, and sacral levels two through four. Now we're gonna resume, just a little bit more information about the spinal cord and its relationship to the vertebral column, which you know is the external bony encasement. What we didn't have a chance to talk about previously are connective protective coverings of the spinal cord. And the brain has the same coverings, but we're not gonna go into that level of detail. These illustrations are essentially identical.

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I'm going to use this one to introduce some terminology. You can use this one to review this information. Um, these are two parts of a vertebral bone. This is dorsal body wall. This is ventral. And by now, you know that we're looking here at a cross section of a spinal cord. And you can see the peripheral white matter, the internal gray matter. Um, two roots, dorsal and ventral. And as I told you, only the dorsal root has a dorsal root ganglion. And here we've created a spinal nerve. I'm going to begin in terms of talking about these coverings. I'm.

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Going to start here, and I'm going to introduce this terminology in a clockwise direction. So here we're pointing to the so called body of the vertebral column. This is the roof, but we're not concerned with that. And now if we move inward from the body of the vertebral bone, what do we encounter first? An epidural space. FAB is outside the outermost connective tissue ensheathment. Bear with me a moment. And it is filled with a copious amount of adipose tissue. Moving inward, what do we find internal to this epidural space? The first

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Of our three connective tissue coverings. This is the dura matter. And actually they can be seen a little bit more clearly here, but I'm going to continue to use this illustration and this pattern of introduction. The dura matter between the dura and the next connective tissue covering, which is the arachnoid matter, there's a subdural space. So we have an outer epidural space. And then between the dura and the second connective ensheathment, we have a subdural space moving progressively inward. The third and most delicate connective tissue ensheathment is the pia monitor, and it lies.

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Directly on the surface of the spinal cord. So we have three protective coverings. These are called meninges. Their composition or structure is most robust in the dura, and they they exhibit a more delicate framework as we go from dora to arachnoid to pia. So pia is the most delicate and as I said a moment ago, is located directly on the surface of the spinal cord. Now finally here, this is a very similar illustration pointing out dorsal gray matter, white matter, dorsal root, ventral root

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Uh, here's our rami, white and gray. Uh, the additional information contained on this slide is simply to show you that your dorsal root and ventral root are in turn formed by a gathering or merging of rootlets, and that rootlets emerge in a single continuous line from the top of the spinal cord down to the bottom. And this is probably the best illustration in terms of understanding the relationship of these paravertebral, vertebral ganglia, white and gray rami, with emerging pairs of spinal nerve. Parts of the vertebral bone, uh, this is a cross-

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Section of the spinal cord, and we're looking at a little bit of its length here. We're encountering our three connective tissue coverings, dora, arachnoe, lupia. And finally here, collection of rootlets on each side, forming a dorsal root with its ganglion, a ventral root here. They merge and form a spinal nerve. And here we see a white ramus and a gray ramus. White ramus, gray ramus. So these rami and their connectivity to paravertebral ganglion, this occurs very close, as I've said many times already this hour, in very close proximity to the vertebral column.

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But notice that individual vertebral ganglia on each side of the vertebral column are connected. And I don't know if that important point emerged in the previous slides. So they they resemble pearl necklaces extending from anterior to or upper to lower extra lengths of the spinal cord. And they're given the term sympathetic chain. So that's that term refers to the connectivity anatomical and functional connectivity of vertebral ganglia extend

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Bending along the length of the vertebral column. Um, I have five minutes left to introduce some new terminology, and then we'll take a break until Thursday. And so I told you that there's a reason why we pay attention to funiculi, dorsal, ventral, and lateral. And that is because we have collections of either a ferrin or a ferrin axons that reside in specific locations in the white matter. One of the new terms today is a tract. A tract is a collection or bundle.

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Of axons that all have their cell bodies of origin in one site. All of the axons derived from these cell bodies then all travel together and terminate and terminate in a second site. So there's a parallel site of origin and site of destination. We will name a tract generally based on the location of the cell bodies and finally the location where their axons terminate. And when we use this information here on Thursday, I will have some good examples of naming of tracks. Now.

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What do we do with tracks? If we assemble two or more tracks in series, we create pathways. Sensory pathways consist of three consecutive tracks, A, B, and C. A motor pathway consists only of two tracks, track one, track two. Since I have three minutes left, I'll proceed on. I've already indicated this is the dorsal funiculus, lateral, and ventral. Now the color coding the artist has used here is he is showing clusters or collections of

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Of axons, which give rise to tracts. And he's using blue to indicate the location of apheret tracts and excuse me, pink or red pink to denote the location of a motor tract. Now let's look at the dorsal funiculus, and we have two here called fascicul- fasciculus cuneatus and gracillus. This deviates from the naming scheme I just told you, so pardon me. But these names have been used for quite a long time, and no one is interested in changing them. But what we can say is the dorsal funiculus contains only sensory tracts. Let's move now to the lab.

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Lateral funiculus. And notice on this side we're seeing several sensory tracts. And let's look at this one. It's called lateral spinothalamic. Lateral tells us it's in the lateral finiculus. Spino tells us the cell bodies of origin are located in the spinal cord. And cerebellum or thalamic, I'm sorry. Spinothalamic tells us that these axons arising in the spinal cord terminate in the thalamus up in the brain. Um, let's look now at the ventral funiculus, anterior spinothalamic cell bodies now.

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Located in the anterior funiculus. Um, locate, yeah. Anterior funiculus of the spinal cord. Axons terminate in the thalassemia. I have just time to introduce one of our motor tracts. Oops. And I'll focus on this one. We're in the lateral funiculus, and we have this rather large collection of axons called lateral corticospinal. The collection of axons is in the lateral funiculus, as you can see, but cortico indicates that the cell bodies are located in the cerebral cortex in the brain. And the fibers descend and terminate in the spinal cord. So we're going to stop here. We'll pick.

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Up this discussion on Thursday. Thank you. Hey, for my brain, feel like I got me wormed. Oh, practice questions have been uploaded. Oh, thank you. Thank you very much. What? See, I see she following us. No, I didn't.0:00

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We have pen issues in Catholic. You know? Are you familiar, or do you do the recall? I did. Yeah. Did you do that? So I just discovered that we have this recurring pen issue, and, again, I can't believe how dependent I am on it. Next time, I will bring a lighting device or something to make this a little easier until we get this rectified. You recall the very last set of topics we covered yesterday was a general overview of the dualistic regulation imposed by parasympathetic arthro

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Called rest and digest, uh, division of the autonomic nervous system, versus the effects of activation of the sympathetic division, which we may refer to as our flight or fight or flight division. Uh, these are generalized statements, uh, information on the slide. As I indicated, please do not refer to the neuroanatomical illustration in the middle, because as I said yesterday, in some aspects, it is less than precise and may actually deviate from better illustrations we've used previously. So at this point-

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I'm going to direct your attention. Now, I have made a few tweaks to this slide compared to what you've downloaded. Okay. So I have also made adjustments to some, uh, text slides that will follow up. I will post these revised slides to Canvas when the lecture is over. Okay. So you're saying, okay, I've seen this slide before, and you're probably getting the idea, well, we're going back to certain imagery and illustrations. And as we're doing this, I'm adding more and more dimensions of information. So at the end of the day, when we're finished talking about the autonomic nervous system.

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You'll be able, for example, to look at this particular illustration, which concerns sympathetic outflow, and you will be able to test yourself or revisit concepts of the neural anatomy, the functionality, and the effect on visceral structures. So for orientation purposes, again, we're looking at the midline brain and spinal cord, as you can see here. And for orientation purposes, the artist is naming by body region and number paired spinal nerves, the C's, the T's, the L's, etcetera. Why do you keep working? It has to be.

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This just happens to me. Sorry. Look at me. Super significant. So on that illustration, midline brain spinal cord for orientation purposes, the naming of consecutive pairs of emerging spinal nerves. We're going to revisit the concepts of the three outflow patterns we discussed on Tuesday. Correct? Number one, number two, number three.

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On the sheer left hand side, if I recall correctly, or before we get to that point, if we look at our spinal cord, notice in direct proximity on either side are interconnected vertebral ganglia, which make up bilateral sympathetic chain. Okay? Now when we look at the sympathetic chain, you're gonna say, okay. You told us that these vertebral ganglia are interconnected on each side of the vertebral column. And in previous illustrations, these vertebral ganglia were the same size and shape. So I want you to take a little bit of a look at this illustration and notice that at surface

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Levels of the sympathetic chain. We see we see instead three enlarged. That's okay. So we'd be good. Thank you. Yeah. Thanks. Well, I'll cross my fingers. If not, you know, where I am, Doctor. Baker. Okay. Thank you. He's only had anything. Okay. Here we go. So little point of clarification. And notice that as we go on, I'm using generalized information or descriptions and nomenclature, but as we take a deeper dive

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I'm going to take time like this to make qualifying statements. Uh, so here, if we look at cervical levels. Oh, come on. Come on. It's not working. I apologize. Okay, I think I can do this verbally. Instead of a series of vertebral ganglia corresponding to every one of the cervical levels of the vertebral column, we instead have three giant ganglia. Whereas at thirva- at thoracic lumbar.

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Sacral coccigial, we have our typical arrangement of one ver, uh, vertebral ganglion per level of the spinal cord. Okay? The importance of this, we will discuss in a moment. Let's get back to our three outflow patterns on the shear left-hand side of this illustration. Uh, what is depicted here by number one, outflow pattern number one, you'll recall that the postganglionic sympathetic neuron exits the spinal cord, reaches the sympathetic chain via the white ramus, correct? Makes synapse within the vertebral ganglion, and sends a postganglionic fiber that uses the great ramus to return to the spinal cord. So we are-

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Looking at outflow here, and again, I apologize. Outflow pattern number one, sympathetic postganglionic fibers to sweat glands, erectile plelea muscle, and smooth muscle associated with peripheral vasculature. Those fibers are brought to those locations by paired spinal nerves, up and down the length of the vertebral column. Now outflow pattern number two was the preganglionic acts on synapsing within a component of the sympathetic chain. And what we're looking at here are synapses in either of these three giant ganglia. Now I'm going to give them a name.

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Superior, middle, and inferior cervical ganglion. Levels T1 through T4, there is also utilization of those local vertebral ganglia to engage in synapse. I have added, as I said before, this additional information. If you wanna take a moment to jot these down. But as I said, I'm gonna upload this revised slide anyway. So if we look at output, postganglionic sympathetic outflow from the superior cervical ganglia, there is massive innervation of a number of different structures associated with the head.

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Pupillary muscle musculature of the eye, innervation of the pineal gland. We'll talk about this next week. Um, and innervation, importantly, of lacrimal glands and our three salivary glands, submandibular, sublingual, and parotid. All of this is accomplished by postganglionic outflow from the superior cervical ganglion. Now, moving down to our next target, which is the heart. And importantly, as I've indicated here, postganglionic outflow is gonna derive from all three of our large cervical ganglia, as well as vertebral ganglia at T1 through T4.

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Moving down to the lungs. This postganglionic outflow occurs from vertebral ganglia at levels T1 through T4. Now outflow pattern number three. Those preganglionics literally bypass the sympathetic chain on each side. They go further into the periphery. They have an opportunity to synapse at one of several prevertebrals. Now you're going to look at this collection of prevertebrals here and say, you only told us there were three. I'm going to only engage with the three primary ones. And I've indicated these.

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By asterisk, celiac ganglion, superior mesenteric ganglion, and finally inferior. There are others. They're smaller, but we're not going to focus on those. So let's continue down with our list of epheren structures. Now we have innervation to the liver and gallbladder and associated bile ducts, stomach, spleen, and pancreas. That postganglionic outflow is derived from the celiac ganglion. Instead, postganglionic outflow from the superior mesenteric ganglion is going to be responsible

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responsible for innervating the ascending colon, transverse colon, and the entirety of the small intestine. And interestingly, outflow then finally from the inferior mesenteric ganglion innervates the descending colon. So this is, um, superior mesenteric provides innervation to certain segments of the colon, but not the entire colon. The final, or I would say next to the final, the descending colon instead outflow from the inferior mesenteric. And finally, we have urinary bladder, external genitalia, and uterus, all deriving postsynaptic innervation from the inferior mesenteric ganglion.

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Oops. Again, the companion illustration, this is very similar to, a cartoon that we discussed in general terms a few days ago. This is out instead our rest and digest autonomic outflow system parasympathetic division. And as on the previous slide, importantly, look at the top because the key is solid line preganglionic, dotted postganglionic. Notice the artist has used blue here to describe sympathetic outflow. And in contrast, on the

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Companion figure using pink, but the same formatting. Solid is preganglionic dotted post. So let's and we have already said that we may alternatively describe the parasympathetic system as the craniosacral outflow. Because recall in the previous slide, sympathetic outflow originates from the lateral horn at level spinal cord levels T1 through L2. Sympathetic outflow instead occurs at two distinctly different regions. You can't get farther apart than the brain versus the sacral level of the spinal cord. After we talk about the autonomic nervous system, we're going to discuss the twelve cranial

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Nerves. Only four of them are engaged in carrying parasympathetic innervation to distinctive effector structures. And as we discussed previously, those are three, seven, nine, and ten. And notice I previously said I'm not gonna ask you to memorize their given names, but I will ask that of you concerning cranial nerve ten, which is the vagus nerve. So I'll be using cranial nerve ten, vagus nerve, those terms interchangeably. So here we have another qualifying statement to make. I told you last time, parasympathetic preganglionic

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Or accents are very long. They travel literally to the wall of the structure to be innervated. This is true for innervation provided by cranial nerve ten and sacral outflow. We kind of have to make a little bit of an exception when we talk about outflow from cranial nerve three, seven, and nine. And that is the focus of these four gray structures. These are ganglia, motor ganglia associated with these cranial nerves. They have names. The ciliary ganglion is where there is pre

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Ganglionic post ganglion ganglionic synapse. And you can see that this provides innervation to the eye, specifically pupillary muscle, the radial muscle. Cranial nerve seven engages in synapse at with at at levels of two different ganglia, pterogopalatine, submandibular. Briefly, cranial nerve seven engages in providing motor commands or directives to the subland sublingual and submaxillary glands, two of our three salivary glands. And finally, cranial nerve nine

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Utilizes the otic ganglion and engages in synaptic contact there with postganglionic neurons that innervate finally the parotid gland, which is the last of our three salivary glands. The last cranial nerve is the vagus nerve, and it has an incredible neuroanatomical pattern of innervation, innervating multiple structures, including the heart, involving input to cardiac muscle cells and controlling the activities of the sinoatrial and atrial ventricular nodes.

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Those are specialized groupings of muscle fibers. They set the tone for contractions in the atria and ventricles respectively. Cranial nerve seven provides innervation to all components of the lower respiratory system. Here in this illustration, we see larynx, trachea, bronchi, and lungs. There is innervation provided to the liver, the gallbladder, and the bile ducts, and also to the stomach. Now outflow from sacral sacral levels of the spinal cord, the preganglionics are called pelvic splank nerves. Now the term splankenic is a very old term.

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It has been used to describe autonomic fibers at the macroscopic or visible level. We may just refer to these as pelvic nerves, but understand it's coming they're derived from cell bodies at sacral levels two, three, and four. Now these fibers, as well as those in cranial nerve ten, as I said a minute ago, travel literally to the walls of the structures to be innervated and there makes synaptic contact with very short postganglionic nerves. So what do our pelvic nerves provide innervation to? As we can see here, ascending, descending colon, small intestine, the rectum,

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Urinary bladder, external genitalia, and uterus. This illustration is very similar to the generalized, uh, cartoon we ended our lecture yesterday talking about. This is basically a rehash of the antagonistic slash dualistic innervation. I'm not going to go through all of this again, but I think this will be or can be a useful slide for review purposes. So this points out the different physiological effects of parasympathetic versus sympathetic innervation, but also introduces some of the neuroanatomical information we have been focusing on.

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For the past couple of days. But again, this is a very good review slide. And now we're going to get into slash physiology pharmacology. You'll recall that we talked about the use of acetylcholine as a transmitter released by parasympathetic postganglionics at the level of the effector cells. We talked instead about norepinephrine, a different neurotransmitter being released from the sympathetic division, specifically postganglionic neurons. And we also made note that only in the sympathetic

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Division is the relative the the principal neurotransmitter, in this case, norepinephrine, is also released in the cir into the circulation by endocrine cells in response to preganglionic sympathetic innervation. So we're going to talk now about these neurotransmitters. And from there, this is kind of our roadmap. From there, we're then going to start talking about the receptors that acetylcholine and norepinephrine utilize to exert relative control or control over different visceral structures. We will introduce the complex topic of diversity.

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Or variety of acetylcholine receptors and norepinephrine receptors, which we will call adrenergic receptors. So we will get there. Our last tool that we will use in talking about the autonomic nervous system is in a separate handout that I posted. And I don't know if you had a chance to look at it when I picked up the document, but it is the table called ANS Autonomic Nervous System. We're going to end up this is our last topic set here. And this is where we're going

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going to, after we have introduced the nomenclature for acetylcholine receptors and norepinephrine/adrenergic receptors, we're going to talk about which subtypes of these receptors exert or impose control over specific organs. So this is where we're headed. So now, uh, our introductory information to lay a foundation for this discussion, we're gonna first talk about cholinergic neurons or neurons that release acetylcholine. We will then segue to adrenergic neurons, namely those that release norepinephrine. So we may define a catecholinergic neuron as a neuron that is capable of releasing-

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Releasing acetylcholine. Again, see, I'm using the abbreviation ACH as a neurotransmitter. We already know that on the parasympathetic side, both the pre and the postganglionics release acetylcholine. Correct? Think back to our generalized slide we discussed the other day. On the sympathetic side, the preganglionics are cholinergic. And as we've discussed many times already yesterday and today, the postganglionics release norepinephrine. We're going to introduce when we get to our table a very interesting deviation from this standard rule. Sympathetic postganglionic innervation

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Of sweat glands is mediated by acetylcholine. So this is a distinction, a differentiation from the neurotransmitter typically used throughout the remainder of the sympathetic bibliography. Now, how do we produce acetylcholine? We're going to utilize two foundational building blocks, namely acetyl CoA and choline. Both of these molecules are transported or introduced into the axon terminal, and it is within the axon terminal that acetylcholine is produced. So it's a local production.

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As you'd expect, our newly synthesized acetylcholine is packaged into synaptic vesicles. And why do we want these molecules packaged and sitting there in a vesicle population? Two important reasons. This packaging prevents inadvertent or premature degradation, so it keeps these newly synthesized molecules safe. And finally, if calcium influx occurs at the axon terminal, there's a cascade of events that will trigger immediate release. So in other words, we can exert control if we have a pre-made, packaged set of vesicles containing acetylcholine.

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Choline. Now some particular agents which can interfere with production of acetylcholine or extrusion of acetylcholine. This is the information presented here at the bottom of the slide. Now hemicollinium is a compound that blocks reuptake of choline into neurons. This will, as you would expect, reduce or decrease a acetylcholine synthesis, ultimately causing a depletion of releasable acetylcholine and downstream diminishing extrusion into the synapse. This

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This introduces a very important concept. Many neurotransmitters, upon release into the synaptic cleft or space, have an opportunity, as you'd expect, to act on receptors on the postsynaptic membrane. As long as neurotransmitter is present in that synaptic cleft, there'll be ongoing stimulation of the postsynaptic membrane. It is inver- it is very important to halt or stop that s- that signaling, and this happens via two mechanisms, which we'll talk about in a minute. One is to retake, re-uptake that released neurotransmitter back into the presynaptic terminal.

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The other important mechanism occurring at the same time is to break down or metabolize that released neurotransmitter within the synaptic cleft. So heavy cholinium, as I just said a minute ago, interferes with reuptake of acetylcholine and as you would expect, is going to impair the production of new releasable neurotransmitter. I've indicated here with three asterisks. Choline is the rate limiting step in acetylcholine synthesis. And if I said reuptake of acetylcholine, pardon me, it is reuptake of choline. So a little misstatement on my behalf. So we have transporters.

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That will recognize choline and take it up from the synaptic cleft, put it back into the presynaptic terminal. And if that process is not interfered with, we can re we can make a new set of acetylcholine molecules. Now botulinum toxin. We've all heard about this, particularly in movies or whatever, but there's an interesting mechanism of action. We understand and we know it to be a highly potent toxin. It will prevent acetylcholine release from the pre presynaptic terminal, causing flaccid paralysis. In other words, musculature, somatic musculature that is unactivated, can affect cardiac function leading to

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heart attack can promote respiratory arrest. We will learn you will learn next semester how voluntary musculature plays an important role in respiration. In other words, introducing air into the lungs and removing CO2. There can be ultimately death. We can use this toxin, although it is possibly lethal. A very tiny clinical dose is established for use as a muscle relaxant in the treatment of severe muscle spasms and overactive bladder. Now magnesium, a bioinorganic element, this interferes with calcium induction of synaptic vessels

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physical excitosis. High toxic doses block acetylcholine release into the synapse. So everything in our body, be it inorganic elements, uh, even protons, pH, everything is maintained within a very narrow homeostatic range. And this is an example of a perturbance of, um, homeostasis. Too little magnesium is not a good thing, and we've learned an example here where excessive amounts of magnesium are not a good thing either. Now, finally, Black Widow spider venom. This induces calcium or promotes calcium influx into the synaptic terminal. Now-

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Now triggering excessive continuous acetylcholine exocytosis resulting in muscle spasms, seizures, now rigid paralysis, and death. Now back to the a topic I introduced a moment ago. The primary mode of acetylcholine inactivation is enzymatic degradation in the synapse. A particular enzyme that is important for this function I have underlined here, acetylcholinesterase. This is a membrane bound enzyme that is expressed both in pre and postsynaptic plasma membrane.

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Approximately ninety percent of acetylcholine is inactivated before it reaches the postsynaptic membrane. So this is, you could consider a level of control of exactly how much acetylcholine after release actually reaches acetylcholine receptors on the postsynaptic membrane. When this degradation occurs, mediated by acetylcholine cholinesterase, a byproduct choline is then taken back up into the turbinal and as I said a few minutes ago, can be utilized to generate new acetylcholine. Acetic acid is used in metabolic

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Pathways within the presynaptic neuron. Now we're going to start talking about pharmacology. We're going to talk about receptors that mediate the effects of acetylcholine. We're going to talk about two general classes of acetylcholine receptors. The first are the nicotinic, which I'm going to introduce on this slide. And the following slide will introduce the second family of receptors, the so called muscarinic receptors. And I'll explain how these families derive their names. If we consider nicotinic receptors, it's been well established.

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established that acetylcholine and the compound nicotine stimulate nicotinic receptors. Nicotine does has no effect on muscarinic receptors. So nicotine nicotine is a highly selective agonist or activator of acetylcholine nicotinic receptors. Now I'm going to subdivide our nicotinic receptors using the abbreviations N1 or N2, but a common term nomenclature system is large capital M small m

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Versus large n, small n small m or small n. These distinguish these subclasses as either the muscle type versus the neuron type. That's the information provided in the small letter. So let's talk about our nm muscle type nicotinic receptors. These are located at the skeletal or voluntary muscle synapse. Skeletal muscles have a specific specialization. It's called a neuromuscular junction. This is where the

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Acetylcholine is introduced and is able to interact with acetylcholine receptors. Um, this particular subtype can be blocked by this neurochemical tubal QR. Now, the neuron type nicotinic acetylcholine receptors are expressed in the central nervous system. They're also present in autonomic postganglionic neurons, and chromium cells in the adrenal medulla also express the NM subtype of nicotinic receptors. This subclass

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Can be blocked by ganglionic blockers, and examples would be an example would be hexomethonium, but their activity is unaffected by tuboccuarate. So we have pharmacologic means to interfere selectively with NM versus N receptor activity. Now important piece of information, and you're going to be coming back to this at many points for the remainder of your pharmacy school curriculum. Acetylcholine nicotinic receptors are

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Ion channel linked, so we call them ionotropic. In other words, when we activate the NM or NN acetylcholine receptors, this will immediately affect ion flux or the flux of specific ions either into or out from the interior of the postsynaptic membrane. And I spoke ahead of myself. Generally, we have the movement of sodium and calcium. Excuse me, ma'am. Yes. Okay. So regarding the negative receptors, you said that what again? Well, before before you before you said there were

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Ion channeling. Could you repeat that? I'm sorry. I was a little over. Yeah. Okay. So what was okay. So what was that comment you made before you said the the receptors are ion channeling? Well, as I say I as I have here in the narrative, activation of this receptor this type of receptor class will affect ion channel activity, opening specific ion channels and ultimately changing the magnitude of movement of sodium and calcium. I'm introducing a new term here and a and a term that you will it will be common knowledge by the time you graduate. We speak of receptors.

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Regardless of the neurotransmitter, if they have a direct effect on ion channel function, in other words, they may be part of the ion channel complex, we call them ionotropic. When we get to the next slide, when I talk about the muscarinics, I'm going to tell you at that point, or I'm telling you now, those are described as metabotropic because they are instead linked to G proteins. So you've already been introduced to the concept of G proteins, right, in your preparatory work. Now once the G protein cascade, and that will involve

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Signaling pathways in the cytoplasm, there can be downstream of metabotropic activation, effect on ion flux. So that is a secondary effect of the activation of the metabotropics. So new terminology, ionotropic versus metabotropic. So our nicotinics are direct directly affect ion channel function and specifically will change the volume of sodium and calcium movement into the cell. And generally, such changes in flux will result

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In a relative depolarization in the vicinity of that ion ion channel on the postsynaptic membrane. So what do we mean by depolarization? What's our resting membrane potential of the neuron? You have this inductive air seven. Seven degrees. Right. So a local change in sodium and calcium in that little vicinity or area can decrease resting membrane potential. So if you activate maybe one receptor, you may actually change it from minus seventy to minus sixty nine. That's still called the depolarization. Now

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Now our other class of acetylcholine receptors, these are our muscarinyx. As you would expect, acetylcholine activates this type of acetylcholine receptor, as does selectively muscarine. So acetylcholine will activate our nicotinex and our muscarinyx, but only nicotine will activate the nicotinex, and only muscarine will activate our muscarinics. Now muscarinic receptors are expressed by central nervous system neurons and visceral efferent target structures, smooth muscle, cardiac muscle,

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Again, our listing of glands, adipose tissue, in the periphery. Now in the middle of the slide, I have now introduced here in a list form five subclasses of muscarinic receptors. So I looked at this the other day, and I thought, you know, I should just start out by saying they're all present in the central nervous system. All of them. But in each case, there are additional unique locations where they are expressed that differentiate them from the other subclasses. So if we look at our m one, not only in the central nervous system, but there are

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Expressed by smooth muscle and glands. M2, myocardial. What do we mean by myocardial? Cardiac skeletal muscle. The pupillary muscle in the eye and certain endocrine glands. Now M3s are also present in the pupil, pupillary muscle. In addition, peripheral arteries, exocrine glands. And finally, M4. Now we have some overlap, some smooth muscle and glands. And finally M5, what makes this subtype unique, they are exclusively present in the central nervous system. Now this is general information. We're going to dive deeper into this.

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And we're going to apply it most usefully when we talk about information in this table. Now, as I said in answer to your question previously, muscarinic receptors are coupled to G proteins. And bear in mind, G proteins can be either stimulatory on cellular functions or inhibitory. So subtypes M one, m three, m five are coupled to stimulatory G proteins. If we activate one or more of this muscarinic subtype, we're going to, as you would expect, increase adenylate cyclase activity

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And secondary to that, we're going to see an uptick in protein kinase A and protein kinase C activity. These are important signaling molecules that you've you've learned about in your preparatory work. Okay. We may say by extension, this activation or induction of stimulatory G protein cascade activity in the cell will generally result in a depolarization or a lessening of the charge across the plasma membrane. And the final new term, I'm gonna finally introduce two the last two terms I'm gonna introduce today. I just said that if we

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Activate a single receptor or a small population of receptors, we're going to create a local change in the plasma membrane potential. If we decrease the potential, say, to go from minus seventy to minus sixty eight, minus sixty seven, that is called an excitatory postsynaptic potential. And all through neuroscience community, that's abbreviated as EPSP. What it means is by activation of a particular type of receptor and affecting ion flux, amongst other things, we're gonna change the the membrane potential. And if we lessen the potential, that

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Considered stimulatory. Because what what does it do? It moves the potential closer to the threshold. What is the threshold? You just said resting potential is minus seventy. What's the threshold for activation of an action potential? Ninety. Fifty. Is it fifty? It can be variable, but I in some sources, including one I generally use, it's, like, minus fifty five. So you have quite a bit of change that must be accomplished. But all of these small local changes can be added together. And if they're sufficient, they can bring you to that level of minus fifty five and trigger a nerve impulse.

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Now M2 and M4 are instead coupled to inhibitory G proteins. These affect potassium and chloride conductance, and changes in those ion fluxes generally causes a exacerbation or increase in negative charge. We call that a hyperpolar polarizing effect, alternatively described as an inhibitory postsynaptic potential or IPSP. The last three minutes, we're going to just introduce now adrenergic receptors.

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Which respond to norepinephrine stimulation. Now sympathetic postganglionic neurons primarily discharge acetylcholine, which I abbreviate as NB. A little bit of background because now we're going to talk about how do we produce norepinephrine. Um, norepinephrine is not the only catecholamine neurotransmitter used by the central nervous system. Uh, it has two others, and they're involved in the same biosynthetic path pathway. The others are dopamine, abbreviated as DA. And finally epinephrine.

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Which is abbreviated here as EPI. Now you know that norepinephrine and epinephrine are both released by the adrenal medulla. Dopamine is synthesized primarily in the central nervous system, but we will find dopamine receptors in the periphery. So what it means is dopamine is produced centrally and carried out by axons to act on receptors in the periphery. Norepinephrine is released within the central nervous system at synapses and as to repeat again also is discharged by postsynaptic symp- postsynaptic sympathetic neurons. Epinephrine instead is primarily released in the brain and only in the periphery by the adrenal medulla. So the last topic.

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For consideration today, we the the the lower half of the slide talks about biosynthesis of catecholamine neurotransmitters. Many neurotransmitters, not all, but a good number are produced from specific amino acids. So in this particular instance, we're going to start with the critical amino acid tyrosine. Now there's an intermediate step where tyrosine is converted to DOPA, and I'm not going to ask you to memorize the full name of DOPA. The abbreviation is sufficient. Let's just consider it a precursor to the third step here, which is the production of dopamine.

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So ultimately, dopamine is derived from tyrosine, and it's interesting to make note, this occurs in the cytoplasm of the axon terminal. Now, two additional steps in this metabolic pathway involve the conversion of dopamine to norepinephrine, and I will ask you to remember this enzyme, dopamine beta hydroxychloroquine. This conversion now occurs in synaptic vesicles. So in other words, when we produce dopamine, we're gonna package it in the vesicles in the axon terminals. Once dopamine is had

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Or packaged within the synaptic vesicle, we may convert it if needed to norepinephrine. The final step in this pathway, which is conversion of norepinephrine to epinephrine. So epinephrine is a metabolite of norepinephrine. This last step or conversion occurs mainly in the adrenal medulla. So in the central nervous system and in nerve most and nerve terminals in the periphery, once we produce norepinephrine, that is no longer manipulated. That is the final product. That is what is released as a signaling molecule.

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But in the adrenal medulla, because we're going to release via endocrine secretion, both norepinephrine and epinephrine, we're going to take those chromophen cells are going to take some of that norepinephrine and convert it to epinephrine. So there's a dual release of those molecules as hormones. Okay. Uh, the last topic. This is very similar to our discussion of acetylcholine once released into the axon terminal. Um, I have three mechanisms here. Reuptake into the axon terminal. In the case of norepinephrine, this is the primary method of an activation. We have specific transporter molecules that.

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Operate as pumps to reintroduce or move cat o- secreted norepinephrine back into the synaptic turbinate. This accounts for fifty to eighty percent of neurotransmitter removal from the synapse. Pump activity inhibited by cocaine and some cyclic depressants, depre- antidepressants. What that means is if we have acetylcholine released and we inhibit or impair the reuptake into the presynaptic structure, we have a continued level, uh, which converge on inappropriate level of continued stimulation. Um, diffusion away from the synapse.

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This is a minor mechanism. This is one of the changes I made. Uh, finally, enzymatic degradation. If we have the norepinephrine present in the synaptic, uh, space, we can utilize two important enzymes. The first is monoamine oxidase, abbreviated as MOA. The second is catechol- o-methyltransferase, a C-O-M-P. I'm gonna stop here. We will revisit the mechanism of action of these two different types of enzymes when we meet again on Tuesday. But notice for both acetylcholine and norepinephrine, uh, the two major mechanisms and the priority-

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Can change from a CO colon to norepinephrine is reuptake or local breakdown of metabolism in the synaptic left. And in both cases, diffusion away from the synapse is a very minor contributing thing. What this tells us is when a transmitter is released into the synapse, there's little opportunity to escape. And the only way that activity can be halted or limited, which is a good thing physiologically, is to break that molecule down or remove it from the synapse. So I will stop here and we'll continue this discussion on Tuesday. That's our next one. Forty six.

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She said tapo mix. Well, I promise you just don't make that right. Yeah. Can you show me which slide that is? That we stopped it. Thirty nine.