Departments of Neurology and Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA.
Science. 2024 Mar;383(6686):967-970. doi: 10.1126/science.adk3863. Epub 2024 Feb 29.
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.
内源性大麻素 (eCB)-介导的抑制性突触抑制作用已被假设，但由于在行为过程中难以跟踪 eCB 动力学和突触可塑性，因此尚未在体内得到证实。在导航线性轨道的小鼠中，我们观察到海马 CA1 位置细胞中位置特异性的 eCB 信号，并且在突触后膜和突触前抑制性轴突中都检测到了这种信号。对突触反应的全光学体内研究表明，突触后去极化后，抑制性突触电位受到抑制。此外，神经元特异性大麻素受体缺失改变了位置细胞的调谐。因此，在行为过程中，快速的、突触后的、活动依赖性 eCB 信号在秒级时间尺度上调节抑制性突触。
