Synapses: from vesicles to circuits

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Synapses from vesicles to circuits
Venkatesh N. Murthy
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Why study synapses?
Something changes!
Input
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Changes most easily seen in developing brain
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How synaptic changes can lead to selective
responses
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How synaptic strength controls neuronal signal
propagation
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What does a synapse look like?
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The machinery of the synapse is complex
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A biased three-part tour of synapses
1. Synaptic vesicle recycling 2. Synaptic
modification 3. Monitoring synaptic activity in
vivo
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Part 1 Synaptic vesicle recycling
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Neurotransmitter release and synaptic vesicles
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Lighting up synapses using fluorescent proteins
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SynaptopHluorin a fluorescent probe
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Transgenic mice expressing synaptopHluorin
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Synaptic activity in living brain tissue
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Exocytosis and endocytosis detected with
synaptopHluorin
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Some new findings using synaptopHluorin
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Not all vesicles at a synapse are the same
100 vesicles
50 vesicles
10 vesicles
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Part 2 Synaptic modification
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How does a synapse form and how is it modified?
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Neural activity can control synapse formation and
modify its strength
But there are other forms of synaptic
modification!
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Using vesicle markers to study synapse formation
and plasticity
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Less active neurons increase their output synapse
number
Ctl
Mut
Kir
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Part 3 Synaptic function in living brains
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Studying first steps in smell the olfactory bulb
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The olfactory bulb
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Synaptic function and modification in the
olfactory system
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SynaptopHluorins expressed in the first synapse
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Imaging odor evoked responses
Adam C. Puche
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Different odors evoke different patterns of
activity
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Olfactory bulb circuits are constructed
postnatally in mice and rats
Glomerular synapses
EPL synapses
Pomeroy, LaMantia and Purves. J. Neurosci. 101952
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Localized activation can be found even in 6 day
old mice
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Comparison of responses to same odors at two ages
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Acknowledgment
Reagents Eduardo Marban Richard Scheller Joshua
Sanes Guo-ping Feng
People Florin Albeanu Shelby Dietz Tomo
Sato Jamie Tyler Zhiying Li Ken Hartman Sumon
Pal Juan Burrone Kathy Vernovsky Sara
Shnider Jamila Newton Cambrian Liu Egle
Cekanaviciute
Support NIH NSF Pew Scholars Program EJLB
Foundation Klingenstein Fund