Transcribed by Tina Park

Thursday, January 23, 2014

Neuroscience Lecture 10 Neurons by Dr. Jean-Pierre Saint-Jeannet Slide 1 Neuroscience: Neurohistology of Nervous System Structure Dr. Jean-Pierre Saint-Jeannet Were going to talk about structure and general organization of the nervous system and histology of the nervous system. This Neuroscience course is the only organ system that has a lecture as a course on its own. In fact it used to be part of multiple courses. Basic Tissue used to be part of Anatomy and Organ System. The lectures you heard from Dr. Jeong used to be part of Anatomy. What Im going to be telling you, which is the histology of nervous system, used to part of basic tissue and then physiology you are going to hear later used to be parts of organ systems but we decided everything would make more sense if we had it together. So today Im going to tell you about histology of the nervous system. Histology means from Greek. Histo- means tissue and -ology means science. So, science of the tissue. Essentially it is the organization of the tissue and composition of different tissues in terms of cell type. Slide 2 Topic Outline Dr. Jean-Pierre Saint-Jeannet So the organization of the next five lectures that I will give you related to that topic are shown here. First well talk about the general organization of the nervous system. Well talk a little bit about the origin of the nervous system. You already heard that a little bit in context of neuroanatomy. Ill tell you a little bit more and then composition of the nervous tissues. That will be essentially our first two lectures today and tomorrow for you I think right at 8. And then the third lecture will be in more detail about specifics of the peripheral nervous system (PNS) and the central nervous system (CNS). Ill try to contrast the two and show you some of the landmarks that allows you to identify the tissue. If it comes from the PNS or rather the CNS. And then at the end well also talk a little bit about the plasticity and regeneration of the nervous system. As you may know the PNS has a stronger capacity to regenerate as compared to the CNS. So well discuss some of that those issues or try to point out to you what are the reasons why this is happening. Well talk a little bit about stem cells and more recent work that has been done in the last two years to try to understand the regenerative property of PNS and CNS. And at the very end, if we have time Ill go over, and I think we should have time, Ill go over a review of the different aspects that I covered in those five lectures Slide 3 Other Textbooks Dr. Jean-Pierre Saint-Jeannet In terms of textbooks, this is one recommended textbook, which is also recommended for Organ Systems and I believe Basic Tissues. So its not specifically dedicated to nervous system but has important chapters on that topic. There are other books that you will find around are as good as this one. This one are available on Vital Books but any other will be fine also. Slide 4 Topic Outline Dr. Jean-Pierre Saint-Jeannet So today I am going to talk about those first general organization of the nervous system, origin of the nervous system, and start talking about the composition of the nervous system.

Slide 5: Neurohistology I & II Dr. Jean-Pierre Saint-Jeannet And Im going to try to stop where I stopped with the first group this morning so we both groups are in sync somewhat. Slide 6 Lecture Outline Dr. Jean-Pierre Saint-Jeannet So first Im going to talk about the organization of the nervous system. The outline of the lecture is shown here. Were going to talk about the organization of the nervous system in terms of anatomy and functional division of the nervous system. Well talk about the origin of the nervous system like I said and talk about the composition of the nervous system. There are two major cell types formed in the nervous system. The neurons, which are the functional units of the nervous system, that are transmitting information and tell you more specifically some of the characteristics of the neuron and histology cross-section and how we can identify them. Another cell type you find in the nervous system, which are quite abundant, is the supporting cell of the nervous system. And then finally well talk about the blood-brain barrier. Slide 7 I - General Organization of the Nervous System Dr. Jean-Pierre Saint-Jeannet So starting from some basic definitions. The function is to receive, interpret, and respond to changes in our external and internal environment. The incoming information is typically analyzed and compared to information that have been stored and also compared to predetermined responses, which are also known as reflex. And this all was for the selection of the most appropriate response to the different conditions Slide 8 A- Anatomical Divisions of the Nervous System Dr. Jean-Pierre Saint-Jeannet The first divisions of the nervous system is anatomical subdivison. So two main parts: CNS, which corresponds to any tissues that is encased in bony structures: brain and spinal cord. Brain being encased in the skull; and spinal cord being encased in spinal column. Everything else is part of the PNS. That includes spinal nerves, there are 31 pairs of those. Cranial nerves, youve heard about cranial nerves right? 12 pairs of those. All the peripheral nerves, ganglia associated with those nerves, and all the specialized nerve endings that will be sensing in the peripherally. Slide 9 B- Functional Divisions of the Nervous System Dr. Jean-Pierre Saint-Jeannet In terms of functional divisions, I mentioned that those receptors, part of the PNS that will sense change in the environment, that will transmit information all the way back through the CNS through afferent neurons, also known as sensory neurons. Sensory neurons, which will convey this information through your interneurons, to motor neurons that are located in the ventral portion of the spinal cord. Ventral neuron that will transmit this information to efferent neuron or motor neuron all the way to effector organs that can be muscles, that can be glands, and so on. Slide 10 CNS and PNS Chart So this is a different representation of it again. Sensory receptors that are in the periphery and they will convey information through the PNS. PNS that measures subdivisions sensory

and motor subdivision. The sensory division through afferent nerve will transmit conveying information where this information will be interpreted and the motor subdivision which involves efferent nerves which will convey the information to the CNS back to the PNS. The motor division of the PNS is further divided in the somatic nervous system (SNS), which is the voluntary nervous system, and the autonomic nervous system (ANS), which is the involuntary nervous system. SNS which will convey information to skeletal muscles to initiate a response. The ANS has two subdivisions: the sympathetic nervous system and parasympathetic nervous systems. The parasympathetic, which is involved in all the body functions and maintain homeostasis of the body and the sympathetic nervous system and the parasympathetic nervous system are, in general, have opposite effects in general. Sympathetic nervous system being involved in the fight or flight response by diverting energy from a function that are inhibited by the parasympathetic nervous system to allow for a specific response. Slide 11 II- Origin of the Nervous System Dr. Jean-Pierre Saint-Jeannet Okay. A few words about the origin of the nervous system. As you know in the developing embryo during gestation, three germ layers will be specified: the ectoderm, the mesoderm, and the endoderm. So the nervous system is derived form the ectoderm layer and generated from the process known as neural induction. Induction is referring to a process that involves two tissues that are adjacent to each otherone that is providing information to the adjacent tissue to change its fate. In this case the neural induction involves the ectoderm and the underlying mesoderm, specifically the caudal mesoderm, axial mesoderm that will send signals to the overlying ectoderm to become neural tissue in specific regions of the ectoderm. Well talk more in terms of the molecular level in term of how this process is taking place. That will be part of the lecture Ill give you in general embryology as part of the Craniofacial biology courses. So this first step is neural induction so you specify your region of the ectoderm to form neural tissue. Then you for the process of neurulation when this tissue that has been induced, which is known as neural plate, will forming not a tube which will give rise to brain and spinal cord. So this neural tube will from into CNS. The PNS on the other hand is not derived from the neural tube directly it is derived form this region that is the boundary between the neural plate and the non-neural ectoderm which is known as the neural crest. Slide 12 Induction of the Neural Plate: Neural Induction Dr. Jean-Pierre Saint-Jeannet So let me show you that on the diagram here looking at the human embryo from dorsal here, anterior here, posterior here. 17 days of gestation. Gastrulating is almost complete; the nervous system has been reduced in this region here. If you make a section for this region here, this is the ectoderm, this is the underlying mesoderm, the axial mesoderm on the notochord. Signal coming form this tissue will induce this region to form the neural plate. At the junction between the neural plate and the non-neural part of the ectoderm you will find this region known as neural crest, which is precursor for PNS. A little bit later, 19 days of gestation, the neural plate that has been induced will start to form into a tube by invagination like this. And will eventually completely close in the same process those two regions adjacent to the neural plate, the neural crest, will come together and fuse.

Slide 13 Function of the Neural Tube: Neurulation Dr. Jean-Pierre Saint-Jeannet That is what is shown here when the process here of closing the neural tube. Those regions of cells that are known as the neural crest, starts to separate form the neural tube and migrate into the embryo. A little bit later, at 22 days of gestation, if we look you look at the trunk level of the neural tube where the neural tube is completely closed. The neural crest has separated from the tissue and the neural crest will give rise to PNS and this [neural tube] will give rise to CNS. Slide 14 Segregation of Ectodermal Derivations Dr. Jean-Pierre Saint-Jeannet So during this process of neurulation there is a process of certain lineage that takes place at the ectoderm there is segregation of what will become the epidermis, skin, from what will become CNS and what will become PNS. And the neural crest that is relevant in this context because it contributes to the PNS but the neural crest and you will hear more about that contributes to many different cell types in your body but well talk about neural crest in only context of all those cells that are part of the PNS. Slide 15 III- Composition of the Nervous System Dr. Jean-Pierre Saint-Jeannet So a few words about the composition of the nervous system. There are two major cell types that you will find: the neurons and the supporting cells. There are very small amount of connection tissues and the CT is highly vascularized. The neurons have a very high demand in oxygen so the deprivation of oxygen for as little as one minute can have a devastating effect on the survival of neurons. Slide 16 A- Neuron Dr. Jean-Pierre Saint-Jeannet So the major cell type of the nervous system in the functional unit of the nervous system is the neuron. So this is here a schematic representation of the neuron. And Im going to try to show you some of the characteristics that can be used to identify the different regions of the neuron and what they do in the histology crosssections. The main region is the cell body, which contains the nucleus. Then you have this axon, which is a projection that comes from the cell body, which conducts the nerve impulse. Then at the end you have synaptic terminals or terminal arborization, which make contact with neighboring cells which can be another neuron or an effector muscle, for example, to allow transmission of this influx. On the other hand, attached to the cell body are dendrites, which detect sense and they are the receptors for change that takes place in the environment. Slide 17 A- Neurons: 1- Functional Components: a- Cell Body Dr. Jean-Pierre Saint-Jeannet Alright lets review some of the different parts in the neuron and some of their characteristics. So the cell body here, which has the region that contains the nucleus, is also sometimes referred to as the perikaryon or the soma. It has a single nucleus, which is typically very lightly stained. Ill show you some examples. There are very large nucleolus that are centrally located in this nucleus. In the cytoplasm that is surrounding the nucleus you will find a number of organelles. Most specifically one type of organelle that is known as nissl bodies, which are sacs of rough endoplasmic reticulum (rER) and really they are the landmarks of the neurons. When you look at histology, the neurons will be the only cell type that contains this structure. So nissl bodies are sacs of

rER meaning that theyre are a lot of protein synthesis taking place. So this is a lot of accumulation of rER so that proteins can be produced. You will find some free ribosomes, mitochondria, large golgi apparatus and vesicles that will be produced at this level that will contain neurotransmitters that are essential for the transmission of nerve impulse. In addition, in this region you will find a number of filaments that are associated with neurons the neurofilaments, which are intermediate filaments, that is only found in neurons and that will provide rigidity to neurons. And youll also find microtubules that will provide strength to the cell. Slide 18 Image: the neuron the only cell that looks back at you Dr. Jean-Pierre Saint-Jeannet This is an example of a black and white stain of the neuron. Just to show you here, the very large nucleus that is very lightly stained and the large nucleoli that is found right in the middle. Sometimes this neuron are refereed as the only cell that looks back at you. It really looks like an eye looking at you. And then you have those accumulations of rER here that correspond to those nissl bodies that I mentioned which are essentially sites of protein synthesis. Depending on the activity of the neuron and depending on how much protein synthesis is taking place, those nissl bodies can be more or less obvious to see on a histology cross-section. Slide 19 Image: Nissl bodies are dilated sacs of RER Dr. Jean-Pierre Saint-Jeannet This is a different view. This is just a diagram here and show you here by EM looking at this nissl bodies showing you the sacs of rER where some of the free ribosomes that are all around, they are really landmarks to identifying neurons. Slide 20 Image: Spinal cord - motor neuron (Pararosaniline-toluidine blue stain) Dr. Jean-Pierre Saint-Jeannet This is a stain here. The name of the stain is not important. In some of my sides you will see stain. Most of them are using a very basic stain, which is called Hematoxylin and Eosin. This one is a little bit different. It is a toluidine blue stain. It is not important to remember the name of the stain. I put them just for reference here. This is staining primarily for the rER, sacs or the nissl bodies that you see in the cytoplasm, all around the nucleus of the cell body. This stain doesnt allow you to discriminate really the neuron from surrounding cell types. So you have a number of supporting cells all around here and some CT. But the stain doesnt allow you to see that. It allows primarily for you to see those nissl bodies. Slide 21 Image: Spinal cord motor neuron (neurofibril staining) Dr. Jean-Pierre Saint-Jeannet This is another stain here, it is a stain that is used specifically to identify a neural filament in the neurons. You can see that the neural filaments are very abundant in the cell body that will not be only found in the cell body but will be found in the projection of the axon and dendrites. This is case of the spinal cord- motor neuron that has stains for those neural filaments. Slide 22 A- Neurons: 1- Functional components: b- Axons Dr. Jean-Pierre Saint-Jeannet Next structure is the axon itself. So this is a long cylindrical process that is anchored at the level of the cell body. And its role is to conduct impulses away from the cell body. The axon in contrast to dendrites, they are smaller projections I

am going to talk about a little bit later. The axon does not contain any cell bodies. That is a way to identify different between axon and dendrites for example. The axon is anchoring the level of the cell body in this region which is a region in which the impulse starts, a region known as axon hillock, and it is a region that is point of attachment to the cell body. The cytoplasm found in the axon is the axoplasm, which is a combination of axon and cytoplasm. The plasma membrane in the axon is referred to as axolemma. And it is not uncommon to find that the main axon will branch out into secondary axon that are known as axon collaterals as you can see here. The terminal arborization of the axon that will make connections with other neurons or other target tissues is this terminal arborization that can have a different name in different textbooks. It can be know as terminal arborization or can be sometimes telodendron. The swollen tips here that are sometimes referred to as terminal boutons of the axon that will actually make the contact with other neurons or other tissues in the body. Slide 23 Spinal Cord Dr. Jean-Pierre Saint-Jeannet So a section there through the spinal cord are these are two motor neurons again. Just to show you again some of those characteristics. So this is the soma here, or the cell body. This is the axon hillock, you can see there is some what of a relatively sharp boundary where the nissl bodies or the darker stain are not present anymore this is the axon hillock here and that is a very good indication and diagnostic to say that this is an axon. This sharp boundary doesnt exist in smaller projections that have dendrites, as you can see here. Slide 24 Image: Spinal Cord Motor Neuron (Hematoxylin/Eosin stain) Dr. Jean-Pierre Saint-Jeannet Another histology cross-section, here for spinal cord - motor neurons. Again to highlight here the very large nucleuolus here and the body not as condense as seen in previous slides for example meaning probably this neuron is not in an extensive phase of protein synthesis. You can still sense the lighter region here, which is the axon hillock here. Its a very good representation that this is very likely to be an axon as compared to those that are more likely to be dendrites. Slide 25 A- Neruons: 1- Functional components: c- Dendrites Dr. Jean-Pierre Saint-Jeannet The third component is the dendrite, which are typically shorter branched projections and are referred to as the dendritic tree. They are receiving external stimuli , convey stimuli to the cell body and then form the cell body all the way to the axon and target tissue. This cytoplasm as I mentioned earlier contain nissl bodies and mitochondria. Also those projection, which can be quite extensive. Well see examples in CNS. For example, poking yourself has very those elaborate dendritic arborizations. Those arborizations carry those structures that are called dendritic spine, gemmule. And this is here, a stain that has been used to visualize the dendritic spines. Those are small protrusions that are presented on the surfaces of dendrites. Slide 26 Image: section of the cerebellum (silver-stained preparation) Dr. Jean-Pierre Saint-Jeannet This is a different stain. Silver stain preparation from one of the cell from cerebellum. You can see some dendritic spines, some of those protrusions of those dendrites.

Slide 27 A- Neurons: 1- Functional components: d- Synapses Dr. Jean-Pierre Saint-Jeannet Those are typically region where connections will be made with adjacent neurons and where synaptic transmission can take place at this level. Alright. So I finished pretty much here with the last group and we will continue tomorrow morning tell you about synapses and characteristics of those synapses. Okay.