Active cortical networks promote shunting fast synaptic inhibition in vivo

Active cortical networks promote shunting fast synaptic inhibition in vivo
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活跃的皮质网络促进体内快速分流突触抑制

DOI:
10.1101/2023.03.01.530641
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发表时间:
2023
期刊:
--
影响因子:
--
通讯作者:
Burman R
Burman R
中科院分区:
--
文献类型:
--
作者:
Burman R

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快速突触抑制决定了哺乳动物大脑中神经元的反应特性,并由氯离子通透性离子型GABA-A受体(GABAARs)介导。尽管它们扮演着基本的角色,但我们仍然不知道GABAARs在完整的大脑中是如何发出信号的。在这里,我们使用vivogramicidin记录来研究在保留天然跨膜氯梯度的条件下,小鼠皮质锥体神经元中的突触GABAAR信号。在麻醉皮质,突触GABA受体发挥经典的超极化效应。相比之下,GABAAR介导的突触信号在清醒的皮质中被发现主要是分流的。这是由于更多的去极化GABA平衡电位(EGABAAR),这被证明是由高水平的突触活动所致,这是清醒皮质网络的特征。在觉醒皮层观察到的突触EGABAAR促进了抑制性输入对局部网络的去同步效应,从而增加了对外部输入的刺激性反应的灵活性。因此,我们的发现表明,GABAAR信号适应于优化皮质功能。
Fast synaptic inhibition determines neuronal response properties in the mammalian brain and is mediated by chloride-permeable ionotropic GABA-A receptors (GABAARs). Despite their fundamental role, it is still not known how GABAARs signal in the intact brain. Here, we usein vivogramicidin recordings to investigate synaptic GABAAR signaling in mouse cortical pyramidal neurons under conditions that preserve native transmembrane chloride gradients. In anesthetized cortex, synaptic GABAARs exert classic hyperpolarizing effects. In contrast, GABAAR-mediated synaptic signaling in awake cortex is found to be predominantly shunting. This is due to more depolarized GABAAR equilibrium potentials (EGABAAR), which are shown to result from the high levels of synaptic activity that characterize awake cortical networks. Synaptic EGABAARobserved in awake cortex facilitates the desynchronizing effects of inhibitory inputs upon local networks, which increases the flexibility of spiking responses to external inputs. Our findings therefore suggest that GABAAR signaling adapts to optimize cortical functions.
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