Retrograde endocannabinoid signaling at inhibitory synapses in vivo

• 成果类型: Article
• 署名作者: Dudok, Barna; Fan, Linlin Z.; Farrell, Jordan S.; Malhotra, Shreya; Homidan, Jesslyn; Kim, Doo Kyung; Wenardy, Celestine; Ramakrishnan, Charu; Li, Yulong; Deisseroth, Karl; Soltesz, Ivan
• 署名单位: Baylor College of Medicine; Baylor College of Medicine; Stanford University; Stanford University; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard Medical School; Stanford University; Peking University; Stanford University; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12478
• DOI: 10.1126/science.adk3863
• 发表日期: 2024-03-01
• 页码: 967-970
• 关键词: hippocampal place cells; endogenous cannabinoids; gaba; cb1; oscillations; RESOLUTION; receptors; DYNAMICS; release; lipase

摘要

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.