Language

English

Publication Date

3-1-2024

Journal

Science

DOI

10.1126/science.adk3863

PMID

38422134

PMCID

PMC10921710

PubMedCentral® Posted Date

3-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Endocannabinoid (eCB)-mediated suppression of inhibitory synapses has been hypothesized, but this has not yet been demonstrated to occur in vivo because of the difficulty in tracking eCB dynamics and synaptic plasticity during behavior. In mice navigating a linear track, we observed location-specific eCB signaling in hippocampal CA1 place cells, and this was detected both in the postsynaptic membrane and the presynaptic inhibitory axons. All-optical in vivo investigation of synaptic responses revealed that postsynaptic depolarization was followed by a suppression of inhibitory synaptic potentials. Furthermore, interneuron-specific cannabinoid receptor deletion altered place cell tuning. Therefore, rapid, postsynaptic, activity-dependent eCB signaling modulates inhibitory synapses on a timescale of seconds during behavior.

Keywords

Animals, Mice, Endocannabinoids, Neuronal Plasticity, Synapses, Synaptic Transmission, Calcium Signaling, CA1 Region, Hippocampal, Inhibitory Postsynaptic Potentials, Receptor, Cannabinoid, CB1, Male, Female, Mice, Knockout

Published Open-Access

yes

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