Effects of GABAA kinetics on cortical population activity: computational studies and physiological confirmations
Effects of GABAA kinetics on cortical population activity: computational studies and physiological confirmations
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DOI：
10.1152/jn.00352.2015
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发表时间：
2016-06-01
影响因子：
2.5
通讯作者：
Chavane, Frederic
中科院分区：
文献类型：
--
作者：
Chemla, Sandrine;Chavane, Frederic
电压敏感染料（VSD）成像产生了前所未有的实时和高分辨率的介观信号来测量皮层群体的活动。我们先前已经表明，神经元隔室对信号的贡献是动态的和刺激依赖性的（Chemla S，Chavane F. Neuronnage 53：420-438，2010）。此外，室间隔缺损信号也会受到网络状态的强烈影响，例如在麻醉与清醒准备中。在这里，我们研究了网络状态的影响，通过GABA（A）受体的调制，室间隔缺损信号使用计算方法。因此，我们系统地测量了GABA（A）介导的抑制性突触后电位（IPSPs）衰减时间常数（TG）对我们模拟的VSD对强度增加的输入刺激的反应的影响。我们的模拟表明，TG强烈调制的VSD信号的动态，影响的幅度，输入响应函数，和瞬态平衡的兴奋和抑制。我们证实了这些预测实验清醒和麻醉的猴子，比较室间隔缺损的反应漂移光栅刺激的各种对比度。最后，一项体外研究表明GABA（A）受体也可能直接受到VSD本身的影响（Mennerick S，Chisari M，Shu H，Taylor A，Vasek M，Eisenman L，Zorumski C. J Neurosci 30：2871-2879，2010）。我们的建模方法表明，本研究中描述的调制类型实际上对群体反应的影响可以忽略不计。这项研究强调，必须谨慎地比较不同技术和网络状态下获得的功能结果。生物物理模型在这里提出了一个足够的工具来描绘VSD数据解释的域。
Voltage-sensitive dye (VSD) imaging produces an unprecedented real-time and high-resolution mesoscopic signal to measure the cortical population activity. We have previously shown that the neuronal compartments contributions to the signal are dynamic and stimulus-dependent (Chemla S, Chavane F. Neuronnage 53: 420-438, 2010). Moreover, the VSD signal can also be strongly affected by the network state, such as in anesthetized vs. awake preparations. Here, we investigated the impact of the network state, through GABA(A) receptors modulation, on the VSD signal using a computational approach. We therefore systematically measured the effect of the GABA(A) mediatedinhibitory post synaptic potentials (IPSPs) decay time constant (TG) on our modeled VSD response to an input stimulus of increasing strength. Our simulations suggest that TG strongly modulates the dynamics of the VSD signal, affecting the amplitude, input response function, and the transient balance of excitation and inhibition. We confirmed these predictions experimentally on awake and anesthetized monkeys, comparing VSD responses to drifting gratings stimuli of various contrasts. Lastly, one in vitro study has suggested that GABA(A) receptors may also be directly affected by the VSDs themselves (Mennerick S, Chisari M, Shu H, Taylor A, Vasek M, Eisenman L, Zorumski C. J Neurosci 30: 2871-2879, 2010). Our modeling approach suggests that the type of modulation described in this study would actually have a negligible influence on the population response. This study highlights that functional results acquired with different techniques and network states must be compared with caution. Biophysical models are proposed here as an adequate tool to delineate the domain of VSD data interpretation.