Li Junlong, Deng Suixin, He Quansheng, Ke Wei, Shu Yousheng
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.
Cereb Cortex. 2021 Mar 5;31(4):2278-2290. doi: 10.1093/cercor/bhaa361.
Autapses are self-synapses of a neuron. Inhibitory autapses in the neocortex release GABA in 2 modes, synchronous release and asynchronous release (AR), providing precise and prolonged self-inhibition, respectively. A subpopulation of neocortical pyramidal cells (PCs) also forms functional autapses, activation of which promotes burst firing by strong unitary autaptic response that reflects synchronous glutamate release. However, it remains unclear whether AR occurs at PC autapses and plays a role in neuronal signaling. We performed whole-cell recordings from layer-5 PCs in slices of mouse prefrontal cortex (PFC). In response to action potential (AP) burst, 63% of PCs showed robust long-lasting autaptic AR, much stronger than synaptic AR between neighboring PCs. The autaptic AR is mediated predominantly by P/Q-type Ca2+ channels, and its strength depends on the intensity of PC activity and the level of residual Ca2+. Further experiments revealed that autaptic AR enhances spiking activities but reduces the temporal precision of post-burst APs. Together, the results show the occurrence of AR at PC autapses, the delayed and persistent glutamate AR causes self-excitation in individual PCs but may desynchronize the autaptic PC population. Thus, glutamatergic autapses should be essential elements in PFC and contribute to cortical information processing.
自突触是神经元的自身突触。新皮层中的抑制性自突触以两种模式释放γ-氨基丁酸（GABA），即同步释放和异步释放（AR），分别提供精确和持久的自身抑制。新皮层锥体神经元（PCs）的一个亚群也形成功能性自突触，其激活通过反映同步谷氨酸释放的强烈单突触自突触反应促进爆发式放电。然而，尚不清楚AR是否发生在PC自突触处并在神经元信号传导中起作用。我们对小鼠前额叶皮层（PFC）切片中的第5层PCs进行了全细胞记录。响应动作电位（AP）爆发，63%的PCs表现出强烈的持久自突触AR，比相邻PCs之间的突触AR要强得多。自突触AR主要由P/Q型Ca2+通道介导，其强度取决于PC活动的强度和残余Ca2+的水平。进一步的实验表明，自突触AR增强了放电活动，但降低了爆发后AP的时间精度。总之，结果表明AR发生在PC自突触处，延迟和持久的谷氨酸AR在单个PCs中引起自我兴奋，但可能使自突触PC群体去同步化。因此，谷氨酸能自突触应该是PFC中的重要元素，并有助于皮层信息处理。
