Title: Neurons :
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4Neurons How they look How we see them
5Nissl-stained brain section
6Santiago Ramon y Cajal
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8Antibody-stained brain section
9Aequorea sp.
10Osamu Shimomura
Aequorea sp.
White light
Black (UV) light
11GFP
12Thy-1 - XFP mice
13YFP-H selectively labels layer 5 pyramids
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16Synapses How they look How we see them
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23You can observe a lot by watching Yogi Berra
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25Sternomastoid muscle
Schaefer
26NMJs are stable in wild type
27Reinnervation of muscle viewed live
28Zebrafish neuromuscular development
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30All Motor Axons Labeled One Motor Axon Labeled
Feng et al , 2000
31Wild-type motor unit
number of terminals 20-40
Wylie
32Multiple XFPs
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35Synaptic takeover
36GYRC3 x CREER TX fixed oculomotor nerve
37TYC9 pup1 (P11-12)
38Sensory Neurons
Feng et al. 2000
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40GYRC3 x CREER TX FV1000 x60 z1.5
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42Synapses How they develop
43Development of the NMJ
44Development of the NMJ
45Synapse formation the big questions
1. Differentiation a. Presynaptic (signals from
the dendrite) b. Postsynaptic (signals from the
axon) 2. Specificity a. How the axon chooses
the right postsynaptic cell b. How the
axon choose the right part of the right
postsynaptic cell 3. Rearrangement How
experience shapes connections
46Synapse formation the big questions
1. Differentiation a. Presynaptic (signals from
the dendrite) b. Postsynaptic (signals from the
axon) 2. Specificity a. How the axon chooses
the right postsynaptic cell b. How the
axon choose the right part of the right
postsynaptic cell 3. Rearrangement How
experience shapes connections
47Clustering of acetylcholine receptors (AChRs)
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49The Anderson and Cohen Experiment
Myocyte
50Anderson and Cohen Conclusions Muscle can
cluster AChRs on its own. But it doesnt nerve
determines location of the postsynaptic
apparatus
51Anderson and Cohen Conclusions Muscle can
cluster AChRs on its own. But it doesnt nerve
determines location of the postsynaptic
apparatus Nerve sends a signal to the muscle
52Anderson Cohen
53Anderson Cohen
54Anderson Cohen
55Anderson Cohen
56Anderson Cohen
57Nerve-derived organizers of postsynaptic
differentiation
Agrin Ascorbic Acid a-CGRP FGF-2 Laminin-1 Midkine
N-CAM Neuregulin Transferrin
58Nerve-derived organizers of postynaptic
differentiation
Agrin Ascorbic Acid a-CGRP FGF-2 Laminin- Midkine
N-CAM Neuregulin Transferrin
59Bioassay for agrin
60Anderson Cohen
X
61The agrin hypothesis
62The knock-out method
63The agrin knockout phenotype
64Agrin is a nerve-derived organizer of
postsynaptic differentiation
65Agrin and Its Receptors
66The Agrin-MuSK-Rapsyn pathway
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69HEK cells
70TYC9 pup3
mCerulean
mEYFP
TDimer2