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DetectSyn: A Rapid, Unbiased Fluorescent Method to Detect Changes in Synapse Density
Published on: July 22, 2022
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Engineered synaptic tools reveal localized cAMP signaling in synapse assembly.
Richard Sando1,2,3, Milan Lyndie Ho1,2, Xinran Liu4
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA.
The Journal of Cell Biology
|December 16, 2021
Summary
New tools called SynTAMs reveal that localized cAMP signaling is crucial for excitatory synapse formation. This signaling is also essential for synapse replacement throughout life.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Synapse formation mechanisms remain incompletely understood.
- Specific signaling pathways organizing initial synapse assembly are unclear.
Purpose of the Study:
- To investigate the role of localized cyclic adenosine monophosphate (cAMP) signaling in postsynaptic specializations during synapse formation.
- To develop novel tools (SynTAMs) for precise manipulation of cAMP signaling.
Main Methods:
- Development of Synaptic Targeting Molecules (SynTAMs) for localized cAMP signaling perturbation.
- Assessment of excitatory and inhibitory synapse formation, neuronal maturation, and dendritic arborization.
- In vivo studies in CA1 neurons and retrograde trans-synaptic rabies virus tracing.
Main Results:
- Localized suppression of postsynaptic cAMP or cAMP-dependent protein kinase activity severely impaired excitatory synapse formation.
- Neuronal maturation, dendritic arborization, and inhibitory synapse formation were unaffected.
- In vivo suppression disrupted specific synapse formations (Schaffer-collateral, entorhinal-CA1/temporoammonic-path).
- Postsynaptic cAMP signaling is required for continuous synapse replacement.
Conclusions:
- Spatially restricted postsynaptic cAMP signals are critical organizers of postsynaptic specialization assembly during synapse formation.
- Postsynaptic latrophilin adhesion-GPCRs, which produce cAMP, are implicated in driving synapse formation.
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