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Neuro: 1:00 - 2:00 Scribe: Ryan O’Neill Monday, January 5, 2009 Proof: Strud Tutwiler Dr. Lester Cytology Page 1 of 4 I. Introduction [S1] a. Going over basic properties of cells in the brain. II. Building Blocks [S2] a. Almost 100 years ago, people didn’t know the basic theory behind the building blocks of the nervous system. b. The most popular theory was the reticular theory, which had the nervous system much like the vasculature (big vessels that became smaller and then went back to larger sizes). c. Golgi-staining techniques were popular during this time and Ramon y Cajal was the big neuroanatomist came up with the idea that there were individual cells in the CNS that were not continuous. d. Today we are going to discuss the different cells in the CNS (the fundamental units of the nervous system). e. Sherrington coined the term “synapse.” III. Learning Objectives [S3] a. Five different learning objectives listed. Exam questions are common to appear within this list. b. ARS [S4] i. There is not an actual answer for this question. IV. Types of cell [S5] a. There are 10x more glial cells than neurons, but they both take up about 50% of the volume of the brain. b. CNS (brain and spinal cord) should not be confused with the PNS (peripheral nervous system). V. Learning Objective #2 [S6] VI. Basic function of a neuron [S7] a. Can generally think of information flowing into and out of a neuron in a particular direction. VII. Parts of a neuron [S8] a. The majority of excitatory information coming to a neuron is collected on dendrites. b. Usually, but not always, pass through the soma and initiate an action potential in the axon and travel down to the terminals and release neurotransmitters. This is the generalized model of how a neuron works. c. Cell body, dendrites and an axon are included. VIII. En masse [S9] a. Stained here are the neuronal cell bodies. b. The axons, which are myelinated, tend to run in tracts. Notice the major white matter tracts. IX. Same but different [S10] a. Neurons are pretty similar. The most common type will have multiple dendrites in the CNS because it tends to integrate a lot of information from a lot of different sources, so it has a lot of synaptic information contacts coming in. b. These most common types (multipolar) also tend to have a single axon leaving the soma, but that axon can form collateral branches. c. Note the pictures of different cell types. i. Bipolar cells – have two main processes; one will be collecting information and one will be outputting information ii. Pseudo-unipolar cells – look like they have a single axon, but then splits and information tends to come from one end and travel to the other end. d. ARS [S11] i. Most of your cortex is made up of these large pyramidal cells. It turns out that these are the cells are in the motor cortex and signal down to the motor neurons in the spinal cord. ii. Purkinje cells are from the cerebellum. X. Pseudounipolar [S12] a. Have dendrites to collect information near the soma and an axon that splits. b. In the PNS, these are the prototypic cells of this sensory system. c. They collect information from the viscera, skin, etc. and bring it into the CNS. i. The cell bodies are in the dorsal root ganglia and come into the dorsal spinal cord. d. A classic example is the sensory fibers. XI. Classes of neurons [S13] a. Also have the motor neurons, which come out of the ventral portion of the spinal cord and go out to the muscles. b. Interneurons are neurons that are very local (ex: fully contained within the spinal cord or within the brain in a specific nucleus) c. Projection neurons in the CNS will project from one nucleus to another or from one part of the cortex to the other (ex: from the frontal lobe to the occipital lobe). XII. Synapses [S14] a. Skipped. Will be discussed later in an entire lecture. XIII. Axons are long [S15] Neuro: 1:00 - 2:00 Scribe: Ryan O’Neill Monday, January 5, 2009 Proof: Strud Tutwiler Dr. Lester Cytology Page 2 of 4 a. Neurons are cells so they have a lot of the same properties of same other cell types except that they are very unique in some ways. b. One of the most unique things about them is a long axon that can be up to 5 feet. c. That axon will contain most of the cytoplasm. This cell has to deal with the fact that it has to synthesize stuff and communicate with other parts of its cell; this is a metabolic demand. d. It also needs a mechanism for signaling from one side of the cell to the other in a fast manner (referred to as the action potential propagation). e. It also has to maintain structure. For a given neuron, axons will be a uniform diameter, so the neuron has to be able to maintain a uniform structure. XIV. Cytoskeleton [S16] a. Neurons use a lot of cytoskeletal elements (e.g. microtubules or microfilaments) b. Cross section of a dendrite [S17] i. There are a lot of structural components in the axon and throughout the neuron because it needs to maintain its dendritic structure as well, so we have these MAPs (microtubule associated proteins) such as Tau (will be mentioned later in reference to cognitive deficits). ii. All of the microtubules and microfilaments will act together to: 1. Maintain the structure of the neuron. 2. Have a dynamic relationship that can retract and withdraw and forming new contacts. XV. Active transport [S18] a. Neurons are not only important structurally, they are also important for communication. b. Within in a cell and between cells of a short distance, diffusion is a great process and extremely fast. c. This is the reason why we can release a chemical from one neuron at a presynaptic terminal and it can communicate very rapidly with the next cell. d. If you want to move several feet by diffusion, it will take extremely too long. A different mechanism is required. Slow and fast transport mechanisms in neurons involve dendrites as well as axons. e. This helps facilitate moving proteins from the soma all the way down to the soma. f. The fast transport is about ½ cm a day (good speed), but it will still take several days. g. The slow transport is not very well understood. h. Things can be moved in different directions, and this has been used to trace neurons with staining dyes. XVI. Ribosomes: Nissl substance [S19] a. It is effective to synthesize most things in the soma because it doesn’t have to go very far. But in dendrites, there are local protein synthesis stations that are important in synaptic contacts where they are changing synaptic strengths (discussed later in the course). There is some evidence that these protein synthesis stations are also present in axons. XVII. Learning Objective #3 [S20] XVIII. High energy use [S21] a. Most ATP is used quickly and a lot of it is consumed by neurons for energy for active transport. b. Lots of protein synthesis is occurring. c. Neurons must maintain these ionic gradients for action potential signaling. d. If there are energy deficits, the neurons are going to be the first to suffer. e. They are exclusively dependent on glucose for their source of ATP. This is going to contrast with glia cells, which can use other sources. XIX. Other organelles [S22] a. There are not many genes that are specific for the brain, but they are unique. b. There is an extensive set of RNA splicing so you can have one gene creating multiple transcripts. c. This is one way in which these cells differ – it’s extensive. There is also a heavier amount of post-translational modification of the proteins (e.g. phosphorylation) that controls their functions. d. Relationship to other cells [S23] i. In the CNS, there are other cells that we need to consider. ii. Endothelial cells, which line the blood vessels, are important for the blood brain barrier. iii. Astrocytes and oligodendrocytes are also within the CNS and will be discussed later. iv. Epydemal cells are a type of glial cell that line the ventricles in which the CSF is produced and moved around the brain to cushion it. v. Neurons, glial cells and these cells listed are the main types of cells. XX. Brain Glue [S24] a. Glial cells are not just “brain glue,” they have specific functions. XXI. Special properties of glia [S25] a. We will be comparing and contrasting glia vs. neurons (see objectives) Neuro: 1:00 - 2:00 Scribe: Ryan O’Neill Monday, January 5, 2009 Proof: Strud Tutwiler Dr. Lester Cytology Page 3 of 4 b. Glial cells have less energy requirements. They function well under anaerobic conditions, so during a stroke glial cells will live and neurons will die. Glial cells will grow where these neurons died off and cause scarring. c. Lack synapses (unlike neurons) and communicate through gap junctions, which are small channels, which allow two cells to communicate. d. Astrocytes (star-shaped) e. LARGELY lack polarity. They are mostly “extracellular space fillers” XXII. Learning Objective #4 [S26] XXIII. Key roles of glia [S27] a. Remove glutamate. i. Glutamate is the principle excitatory transmitter in the brain. ii. If it were not removed efficiently, it would become cytotoxic. b. Myelination. c. Homeostasis. i. Ex: taking up extracellular potassium because these levels are low outside (extracellular fluids) and in the CSF because too much potassium means we have too much excitability. d. Unlike neurons, they can divide. XXIV. Classification [S28] a. Will discuss classification, different types, and functions and relate them to how they interact with neurons. b. General classification: macroglia vs. microglia c. All you need to know is that microglia are more like phagocytes and macrophages. i. Found more in an immune-type cell. XXV. Microglia [S29] XXVI. Radial glia [S30] a. Guidance cells so that the nervous system develops correctly, so that neurons can follow a migratory path. b. This can result in a lot of developmental problems if the cortex is not developing properly. XXVII. Learning Objective #5 [S31] a. Just know these brief things about microglia and radial glia. b. We will mostly focus on astrocytes, Schwann and oligodendrocytes. c. Do not worry about the differences between the types of astrocytes because functionally they have the same role. d. Schwann cells and oligodendrocytes both have the same major role: myelination. XXVIII. Schwann cell [S32] a. PNS b. Form myelin sheets that wrap around the axons. c. BIG difference between Schwann cells and oligodendrocytes: Schwann cells only contact one axon, but an axon needs multiple Schwann cells to insulate its whole length. d. Myelin sheet [S33] i. Myelination insulates the axons to speed up action potential propagation so faster signaling can occur. ii. Without myelination, there wouldn’t be enough space in your skull to put all of the axons because their diameters would have to be so wide. iii. The speed of propagation through an unmyelinated axon is proportional to its diameter. e. Gap junctions and disease [S34] i. If you take an axon and wrap around a myelin sheet, how can the cell get something from the soma to the inner sheet? It would have to go around and around the sheet. But instead it uses these gap junctions, which glial cells use to talk to each other with, in order to talk to its different layers of membrane. ii. It can get nutrients from the soma and bypass the layers. iii. There are human mutations in these channels that lead to demyelination and neuropathies. f. Nodes of Ranvier [S35] i. Where the individual Schwann cells meet and leave a space. XXIX. Oligodendrocytes [S36] a. CNS b. Same role as Schwann cells. Wrap around axons multiple times. c. An oligodendrocyte can actually wrap around multiple axons. In the CNS, there are more space constraints and you need to conserve what space is available. d. 1:10 to 1:50 [S37] i. Oligodendrocytes can do up to 50 axons, so if you have damage to these cells you are going to take out a lot of axons as well. XXX. Unmyelinated CNS fibers [S38] a. Not all axons are myelinated (e.g. local interneurons and major projection neurons) Neuro: 1:00 - 2:00 Scribe: Ryan O’Neill Monday, January 5, 2009 Proof: Strud Tutwiler Dr. Lester Cytology Page 4 of 4 XXXI. CNS vs. PNS summary [S39] a. Diagram from the book. Shows inside the CNS and the PNS. Take a look at it in the book! b. Look at which cells are in the CNS and in the PNS. c. A motor neuron starts in the CNS. d. Inside the CNS, the myelination is by oligodendrocytes, but outside the CNS its myelination is Schwann cells. XXXII. Astrocytic end feet [S40] a. Last type of cells in this group: Astrocytes. b. Contact blood vessels, as well as neurons. c. Induce the blood-brain-barrier [S41] i. CRITICAL for inducing the blood brain barrier. Huge role! ii. This barrier stops many substances from getting to the brain. iii. They get the endothelial cells to form very tight junctions and decrease leakage. iv. One area of usual high leakage is the brain stem close to your vomiting center, so your brain can detect if you are getting poisoned for example. d. From here to there [S42] i. Here we have glial cells that contact capillaries and neurons. ii. This is where a polarity aspect of glial cells could exist because they are in a prime position to move things away from neurons and into the blood or vice versa. e. Buffering of extracellular ions [S43] i. Also has a metabolic role. ii. When neurons signal action potentials, a movement of sodium into the cell and potassium out of the cell occur. iii. Remember potassium is low outside the cell. iv. If potassium levels go up, cells will be depolarized and be overexcited. v. One function of glia is to clean this up. vi. Around neurons they could remove potassium and it would diffuse and end up in the capillaries. This is just a hypothesis of what could be occurring. f. Astrocytes are not really star-shaped [S44] i. Remember, there is very little extracellular space. ii. Glial cells occupy non-overlapping territories so it can maintain its duties of soaking up potassium or glutamate and cover a lot of space and not let any part of the brain not have this function. iii. Are not really star-shaped. g. Transmitter “shuttle” [S45] i. Skipped? XXXIII. Nervous system regeneration [S46] a. The CNS does not regenerate. b. If you damage an axon in the PNS, it will re-grow and re-innervate structures. i. The main mechanism is a glial cell that promotes regeneration in the PNS, but actively represses regeneration in the CNS. XXXIV. Glia verses neuron – difference? a. One of the main distinctions between neurons and glia. Neurons are the ones that do the fast signaling and glial cells are not excitable cells. They do have some channels, but are not excitable in the way that we think of neurons. [End 38:30 min]