Determination of effective synaptic conductances using somatic voltage clamp
Determination of effective synaptic conductances using somatic voltage clamp
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使用体细胞电压钳测定有效突触电导
DOI：
10.1371/journal.pcbi.1006871
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发表时间：
2017-10
影响因子：
4.3
通讯作者：
Cai David
中科院分区：
文献类型：
--
作者：
Li Songting;Liu Nan;Yao Li;Zhang Xiaohui;Zhou Douglas;Cai David
兴奋性和抑制性神经元之间的相互作用赋予大脑丰富的功能。为了理解神经元计算背后的突触机制，一个基本方法是研究每个神经元的兴奋性和抑制性突触输入的动力学。确定输入电导的传统方法已经应用了数十年，它采用通过电压钳获得的突触电流-电压 (I-V) 关系。由于空间钳效应，测量的电导与枝晶上的局部电导不同。因此，测量电导的解释仍有待澄清。通过理论分析、电生理实验和现实神经元模拟，我们证明了由于传统方法忽略了钳位电流和突触电流之间的非线性相互作用，局部电导与传统方法测量的电导之间不存在变换。因此，传统方法确定的电导可能与树突上的局部电导不相关，并且如实验中观察到的，其值可能在物理上为负值。为了规避空间钳效应的挑战并阐明突触对神经元信息处理的影响，我们提出了有效电导的概念，它与树突上的局部电导成正比，直接反映了突触输入对体膜电位动态的功能影响，并进一步开发了一个准确确定有效电导的框架。我们的工作建议重新审视以前涉及电导测量的研究，并提供一种可靠的方法来评估突触对神经元计算的影响。
The interplay between excitatory and inhibitory neurons imparts rich functions of the brain. To understand the synaptic mechanisms underlying neuronal computations, a fundamental approach is to study the dynamics of excitatory and inhibitory synaptic inputs of each neuron. The traditional method of determining input conductance, which has been applied for decades, employs the synaptic current-voltage (I-V) relation obtained via voltage clamp. Due to the space clamp effect, the measured conductance is different from the local conductance on the dendrites. Therefore, the interpretation of the measured conductance remains to be clarified. Using theoretical analysis, electrophysiological experiments, and realistic neuron simulations, here we demonstrate that there does not exist a transform between the local conductance and the conductance measured by the traditional method, due to the neglect of a nonlinear interaction between the clamp current and the synaptic current in the traditional method. Consequently, the conductance determined by the traditional method may not correlate with the local conductance on the dendrites, and its value could be unphysically negative as observed in experiment. To circumvent the challenge of the space clamp effect and elucidate synaptic impact on neuronal information processing, we propose the concept of effective conductance which is proportional to the local conductance on the dendrite and reflects directly the functional influence of synaptic inputs on somatic membrane potential dynamics, and we further develop a framework to determine the effective conductance accurately. Our work suggests re-examination of previous studies involving conductance measurement and provides a reliable approach to assess synaptic influence on neuronal computation.
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