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Updated: Nov 7, 2025
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An Optical Assay for Synaptic Vesicle Recycling in Cultured Neurons Overexpressing Presynaptic Proteins
Published on: June 26, 2018
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Cannabinoid receptor activation acutely increases synaptic vesicle numbers by activating synapsins in human synapses
Christopher Patzke1,2, Jinye Dai3,4, Marisa M Brockmann5
1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA. cpatzke@nd.edu.
Molecular Psychiatry
|May 1, 2021
Summary
Cannabinoid drugs, like cannabis, regulate brain function by affecting presynaptic CB1 receptors (CB1Rs). This study reveals CB1R activation rapidly mobilizes synaptic vesicles via synapsin-1, impacting neurotransmitter release.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Cannabis and cannabinoid drugs are widely used recreationally and therapeutically.
- Cannabinoids primarily act via presynaptic CB1 receptors (CB1Rs), abundant G-protein-coupled receptors in the brain.
- CB1R activation is known to decrease neurotransmitter release and induce long-term plasticity.
Purpose of the Study:
- To identify novel mechanisms of acute cannabinoid signaling in presynaptic terminals.
- To investigate the regulation of synaptic vesicle pools by CB1R activation.
- To elucidate the role of synapsins in cannabinoid-mediated neuromodulation.
Main Methods:
- Utilized human and mouse neurons for experiments.
- Employed conditional deletion of synapsin-1 to assess its contribution.
- Used Gi-DREADD hM4D activation to mimic CB1R effects.
Main Results:
- CB1R activation rapidly recruits synaptic vesicles to nerve terminals.
- This recruitment is mediated by the suppression of cAMP-dependent synapsin phosphorylation.
- Synapsin-1 plays a significant role in the CB1R-dependent regulation of neurotransmission.
- Gi-DREADD activation mimicked CB1R effects in a synapsin-1-dependent manner.
Conclusions:
- Uncovered a novel CB1R-dependent presynaptic mechanism regulating synaptic vesicle organization.
- Demonstrated that synapsin-1 phosphorylation is a key mediator of cannabinoid effects on neurotransmission.
- Highlighted synapsin-1 phosphorylation as a general presynaptic mechanism for neuromodulation.
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