L4 - Lecture 4: Synapse formation and maturation at NMJ...

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Unformatted text preview: Lecture 4: Synapse formation and maturation at NMJ (outline) I. Why NMJ? II. Formation and stabilization for NMJs during development. III. Activity dependent synapse elimination. Required reading: Lictmann and Sanes review papers. Notes: Printing with black background http://www.cadforum.cz/cadforum_en/qaID.asp?tip=4513 Why NMJs? 1. Big and simple: NMJs are approximately 1000 times larger than synapses in the brain; Sanes and Lichtman, 2001 Why NMJs? 2. Accessibility: easy to access and expose for imaging or manipulation; Van Mier, Balice-Gordon and Lichtman, 1994 Why NMJs? 2. Accessibility: easy to access and expose for imaging or manipulation; Feng, Lichtman & Sanes Why NMJs? 3. Different ways to examine: electrophysiology, in vivo imaging, molecular examination and ultrastructural studies; MEPP and evoke potential, Frog NMJ Fatt and Katz, 1950 Nature Synaptic vesicle recycling, Frog NMJ Heuser and Reese, 1973, J Cell Biol Why NMJs? 4. Best knowledge: the structural organization and molecular components have already been well studied at NMJs. Why NMJs? 5. Similarity rules as CNS synapses. eg. synapse elimination Cajals drawing Scanning EM Why NMJs? Finally, it is a beautifully system to study ! An mature NMJs Presynaptic : clusters of synaptic vesicles (contain neurotransmitter ACh) at active zones. Also enrich in mitochondria energy source. Postsynaptic : clusters of AChRs, Na channels, junctional folds. There is a precise alignment of pre and post-synaptic sites. Synaptic cleft : contain extracellular materials, such as basal laminin, AChE. Schwann cells (SCs) : myelinating SCs insulate the axon, while terminal SCs cover the synapse sites. Terminal Schwann cells (TSCs) precisely cover nerve terminals at adult mouse NMJ AChR Axon Schwann cell Origin of each NMJ component Myoblasts (later myotubes) from the somite, Motor axons from the neural tube, Schwann cells from the neural crest. All three cells travel long distances to meet at the NMJ Stages in developmental NMJs 1. A growth cone approaches to newly formed myotube. 2. Formation of a morphologically unspecialized but functional contact. 3. Terminal accumulate synaptic vesicles and formation of basal lamina in synaptic cleft. Stages in developmental NMJs 1. A growth cone approaches to newly formed myotube 2. Formation of a morphologically unspecialized but functional contact. 3. Terminal accumulate synaptic vesicles and formation of basal lamina in synaptic cleft. 4. AChRs cluster postsynaptically. Muscle mature, multiple axons converge on a single site. Schwann cells follow axons to NMJs....
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L4 - Lecture 4: Synapse formation and maturation at NMJ...

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