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NEUROCYTOLOGY Sept. 2, 2009 Jennifer LaVail, Ph.D. (http://anatomy.ucsf.edu/Pages/lavaillab/index.html) Objectives NEUROCYTOLOGY To build on your understanding of the structure and diversity of the cells that make up the nervous system 1. Structure and function of neurons 2. Axoplasmic transport 3. Structure and function of synapses 4. Structure and function of glial cells What kinds of cells are these? What kinds of cells are these? Neuron? Epithelial cell? Glial cell? What makes a neuron special? The neuron has the same biochemistry and complement of organelles as other cells of the body. But, neurons are remarkable for their polarity. Structurally the two most distinctive features of the neuron are its polarized shape and localized secretory function. Polarized shape - Action potential Among all the cells in our body, only neurons have axons. The axon requires unusual modifications of the cytoskeleton and specialized intracellular transport mechanisms. Action potential Microtubule polarity Microtubule polarity Fibroblasts have continuous µts. Fibroblasts have unipolar µts. Neurons have multiple µts. Axons have unipolar µts. Dendritic µts have mixed polarity. Soma The neuron cell body is the primary location of protein synthesis. Most of the proteins for axon maintenance and synaptic function have to be transported to the axon. Where is the cell body? What is special about this neuron cell body? Electron micrograph of a neuronal cell body Cytoplasm = pink; nucleus = yellow Electron micrograph of Nissl bodies (stacks of RER) “protein synthesis machines” Neuron cell body also has polarity axon hillock - region with no ribosomes…beginning of the axon. DRG axon hillock Neuronal polarity Dendrites Input region of neuron Dendrites py ramidal-Purkinje Form of energy varies, e.g., chemical, stretch, thermal, neurochemical. Integrates excitatory and inhibitory synaptic inputs. Principal structures of a neuron processes Cell Body Dendrites Axon hillock Initial Segment Axon Synaptic terminals Pyramidal neuron, rat cerebral cortex Blowfly neuron Motoneuron axons grow long distances to muscle endplateso The structure of chemical synapses Motor end plate 2 Neuromuscular junction in Lateral rectus muscle Chemical Synapse Voltage-sensitive calcium channels Synaptic cleft 15-100 nm CNS synapses sy napse Synaptic components: Synaptic vesicles Presynaptic membrane Synaptic cleft Postsynaptic membrane Two large synaptic terminals containing mitochondria contacting a dendrite A synaptic terminal containing dense cored vesicle indicating the presence of catecholamine transmitters A large dendrite and spine contacted by many synaptic boutons Distinguishing characteristics of axons and dendrites Characteristic Axon Dendrite Ontogeny develops early develops later Length several µm to >1 m limited Size/Shape 0.1 to 20 µm uniform diameter 0.1 – 5 µm tapered Axon hillock present absent RER absent present Cytoplasm vol. 100 x greater relatively little Number per neuron 1 >1 Excitability conducts AP passive spread Myelin present on axons >than 1 um rare but glial wrap Major Point: Mature axon has no RER, ribosomes, Golgi, so no way to make proteins. Proteins have to be transported into and along axon. giraffe Neuron cell body ~100 µm Embryonic neurons move, axons grow. Motile embry onic neuron Differentiating neuronal cells (actin, microtubules and DNA) Torsten Wittman The components of axonal transport Axonal transport cargo motor microtubules Cargo comprised of protein, peptides, proteoglycans and amino acids. Most are transported within organelles. (No synaptic vesicle transport). Rates are about 200-400 mm/day or much slower, 1-2 mm/day. Bidirectional movement depends on balance of cytoplasmic motors. Real time assays of viral transport QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. QuickTime™ and a Sorenson Video decompressor are needed to see this picture. Anterograde transport of HSV Axonal transport of virus HSV transport The myelin sheath along a myelinated CNS axon is composed of sections of myelin made from a number of individual cells Remember, however, not all axons are myelinated. Small diameter axons generally have no myelin covering. Axon PNS In the PNS axons less than 1 µm in diameter are unmyelinated. RELATIVE SIZES Structure (mm) Visual Cortex (thickness) 5 Cortical column (thickness) 0.25 Neuron cell body Red blood cell Neuromuscular junction Sympathetic axon CNS synaptic bouton Dense core synaptic vesicle Synaptic vesicle Smooth endoplasmic reticulum µm 250 15-100 7 2-4 0.2 0.5-2.0 nm 200 500-2000 100 50 5