Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Undergraduate program, Indian Institute of Science, Bangalore, India.
Sci Rep. 2020 Jan 15;10(1):374. doi: 10.1038/s41598-019-57243-8.
Hippocampal pyramidal neurons are endowed with signature excitability characteristics, exhibit theta-frequency selectivity - manifesting as impedance resonance and as a band-pass structure in the spike-triggered average (STA) - and coincidence detection tuned for gamma-frequency inputs. Are there specific constraints on molecular-scale (ion channel) properties in the concomitant emergence of cellular-scale encoding (feature detection and selectivity) and excitability characteristics? Here, we employed a biophysically-constrained unbiased stochastic search strategy involving thousands of conductance-based models, spanning 11 active ion channels, to assess the concomitant emergence of 14 different electrophysiological measurements. Despite the strong biophysical and physiological constraints, we found models that were similar in terms of their spectral selectivity, operating mode along the integrator-coincidence detection continuum and intrinsic excitability characteristics. The parametric combinations that resulted in these functionally similar models were non-unique with weak pair-wise correlations. Employing virtual knockout of individual ion channels in these functionally similar models, we found a many-to-many relationship between channels and physiological characteristics to mediate this degeneracy, and predicted a dominant role for HCN and transient potassium channels in regulating hippocampal neuronal STA. Our analyses reveals the expression of degeneracy, that results from synergistic interactions among disparate channel components, in the concomitant emergence of neuronal excitability and encoding characteristics.
海马锥体神经元具有特征性的兴奋性特征，表现出θ频率选择性 - 表现为阻抗共振和尖峰触发平均（STA）中的带通结构 - 以及针对γ频率输入的一致性检测调谐。在细胞尺度编码（特征检测和选择性）和兴奋性特征的同时出现中，分子尺度（离子通道）特性是否存在特定的限制？在这里，我们采用了一种具有生物物理约束的无偏随机搜索策略，涉及数千个基于电导率的模型，涵盖 11 种活跃的离子通道，以评估 14 种不同的电生理测量同时出现的情况。尽管存在强烈的生物物理和生理限制，但我们发现了在频谱选择性、沿着积分器-一致性检测连续体的工作模式以及固有兴奋性特征方面相似的模型。导致这些功能相似模型的参数组合不是唯一的，彼此之间相关性较弱。在这些功能相似的模型中，我们对单个离子通道进行虚拟敲除，发现通道和生理特征之间存在多对多关系，以介导这种简并性，并预测 HCN 和瞬时钾通道在调节海马神经元 STA 方面发挥主导作用。我们的分析揭示了来自不同通道成分协同相互作用的简并性的表达，这种表达存在于神经元兴奋性和编码特征的同时出现中。
