Mishra Poonam, Narayanan Rishikesh
Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
Curr Res Neurobiol. 2021 Mar 5;2:100007. doi: 10.1016/j.crneur.2021.100007. eCollection 2021.
Heterogeneities in biological neural circuits manifest in afferent connectivity as well as in local-circuit components such as neuronal excitability, neural structure and local synaptic strengths. The expression of adult neurogenesis in the dentate gyrus (DG) amplifies local-circuit heterogeneities and guides heterogeneities in afferent connectivity. How do neurons and their networks endowed with these distinct forms of heterogeneities respond to perturbations to individual ion channels, which are known to change under several physiological and pathophysiological conditions? We sequentially traversed the ion channels-neurons-network scales and assessed the impact of eliminating individual ion channels on conductance-based neuronal and network models endowed with disparate local-circuit and afferent heterogeneities. We found that many ion channels differentially contributed to specific neuronal or network measurements, and the elimination of any given ion channel altered several functional measurements. We then quantified the impact of ion-channel elimination on response decorrelation, a well-established metric to assess the ability of neurons in a network to convey complementary information, in DG networks endowed with different forms of heterogeneities. Notably, we found that networks constructed with structurally immature neurons exhibited functional robustness, manifesting as minimal changes in response decorrelation in the face of ion-channel elimination. Importantly, the average change in output correlation was dependent on the eliminated ion channel but invariant to input correlation. Our analyses suggest that neurogenesis-driven structural heterogeneities could assist the DG network in providing functional resilience to molecular perturbations.
生物神经回路的异质性表现在传入连接以及局部回路组件中，如神经元兴奋性、神经结构和局部突触强度。齿状回（DG）中成年神经发生的表达放大了局部回路的异质性，并引导传入连接的异质性。赋予这些不同形式异质性的神经元及其网络如何响应单个离子通道的扰动？已知在几种生理和病理生理条件下，单个离子通道会发生变化。我们依次跨越离子通道、神经元和网络尺度，评估消除单个离子通道对具有不同局部回路和传入异质性的基于电导的神经元和网络模型的影响。我们发现，许多离子通道对特定的神经元或网络测量有不同的贡献，消除任何给定的离子通道都会改变几种功能测量。然后，我们量化了离子通道消除对响应去相关的影响，响应去相关是一种成熟的指标，用于评估网络中神经元传递互补信息的能力，该指标应用于具有不同形式异质性的DG网络。值得注意的是，我们发现由结构不成熟的神经元构建的网络表现出功能稳健性，即在面对离子通道消除时，响应去相关的变化最小。重要的是，输出相关性的平均变化取决于被消除的离子通道，而与输入相关性无关。我们的分析表明，神经发生驱动的结构异质性可以帮助DG网络为分子扰动提供功能弹性。
