Department of Neurosciences, Case Western Reserve University, Cleveland, United States.
Elife. 2019 Apr 29;8:e44954. doi: 10.7554/eLife.44954.
Most neurons do not simply convert inputs into firing rates. Instead, moment-to-moment firing rates reflect interactions between synaptic inputs and intrinsic currents. Few studies investigated how intrinsic currents function together to modulate output discharges and which of the currents attenuated by synthetic cholinergic ligands are actually modulated by endogenous acetylcholine (ACh). In this study we optogenetically stimulated cholinergic fibers in rat neocortex and find that ACh enhances excitability by reducing Ether-à-go-go Related Gene (ERG) K current. We find ERG mediates the late phase of spike-frequency adaptation in pyramidal cells and is recruited later than both SK and M currents. Attenuation of ERG during coincident depolarization and ACh release leads to reduced late phase spike-frequency adaptation and persistent firing. In neuronal ensembles, attenuating ERG enhanced signal-to-noise ratios and reduced signal correlation, suggesting that these two hallmarks of cholinergic function in vivo may result from modulation of intrinsic properties.
大多数神经元并非简单地将输入转化为发放频率。相反，神经元的发放频率实时反映了突触输入和内在电流之间的相互作用。很少有研究调查内在电流如何协同调节输出放电，以及哪些由合成胆碱能配体衰减的电流实际上受到内源性乙酰胆碱 (ACh) 的调节。在这项研究中，我们在大鼠新皮层中光遗传学刺激胆碱能纤维，发现 ACh 通过减少 Ether-à-go-go Related Gene (ERG) K 电流来增强兴奋性。我们发现 ERG 介导了锥体神经元中尖峰频率适应的晚期阶段，并且比 SK 和 M 电流招募得更晚。在同时去极化和 ACh 释放期间衰减 ERG 会导致尖峰频率适应的晚期阶段减少和持续放电。在神经元集合中，衰减 ERG 会增强信噪比并降低信号相关性，这表明体内胆碱能功能的这两个标志可能是由于内在特性的调节所致。
