论局部皮质网络中兴奋与抑制整体平衡的生理和结构因素。

On the physiological and structural contributors to the overall balance of excitation and inhibition in local cortical networks.

机构信息

School of Mathematics, Georgia Institute of Technology, Atlanta, 30332, Georgia, USA.

出版信息

J Comput Neurosci. 2024 Feb;52(1):73-107. doi: 10.1007/s10827-023-00863-x. Epub 2023 Oct 14.

Abstract

Overall balance of excitation and inhibition in cortical networks is central to their functionality and normal operation. Such orchestrated co-evolution of excitation and inhibition is established through convoluted local interactions between neurons, which are organized by specific network connectivity structures and are dynamically controlled by modulating synaptic activities. Therefore, identifying how such structural and physiological factors contribute to establishment of overall balance of excitation and inhibition is crucial in understanding the homeostatic plasticity mechanisms that regulate the balance. We use biologically plausible mathematical models to extensively study the effects of multiple key factors on overall balance of a network. We characterize a network's baseline balanced state by certain functional properties, and demonstrate how variations in physiological and structural parameters of the network deviate this balance and, in particular, result in transitions in spontaneous activity of the network to high-amplitude slow oscillatory regimes. We show that deviations from the reference balanced state can be continuously quantified by measuring the ratio of mean excitatory to mean inhibitory synaptic conductances in the network. Our results suggest that the commonly observed ratio of the number of inhibitory to the number of excitatory neurons in local cortical networks is almost optimal for their stability and excitability. Moreover, the values of inhibitory synaptic decay time constants and density of inhibitory-to-inhibitory network connectivity are critical to overall balance and stability of cortical networks. However, network stability in our results is sufficiently robust against modulations of synaptic quantal conductances, as required by their role in learning and memory. Our study based on extensive bifurcation analyses thus reveal the functional optimality and criticality of structural and physiological parameters in establishing the baseline operating state of local cortical networks.

摘要

皮质网络中兴奋和抑制的总体平衡对于其功能和正常运作至关重要。这种兴奋和抑制的协同进化是通过神经元之间复杂的局部相互作用建立的,这些相互作用由特定的网络连接结构组织,并通过调节突触活动进行动态控制。因此,确定这些结构和生理因素如何有助于建立兴奋和抑制的总体平衡对于理解调节平衡的稳态可塑性机制至关重要。我们使用具有生物学合理性的数学模型来广泛研究多个关键因素对网络总体平衡的影响。我们通过某些功能特性来描述网络的基线平衡状态,并展示网络的生理和结构参数变化如何偏离这种平衡,特别是导致网络的自发活动向高振幅慢振荡状态转变。我们表明,可以通过测量网络中平均兴奋性和平均抑制性突触电导的比值来连续量化对参考平衡状态的偏差。我们的结果表明,局部皮质网络中抑制性神经元与兴奋性神经元数量的常见比值对于其稳定性和兴奋性几乎是最优的。此外,抑制性突触衰减时间常数和抑制性-抑制性网络连接密度的值对于皮质网络的总体平衡和稳定性至关重要。然而,我们的结果表明,网络稳定性对于突触量子电导的调制具有足够的鲁棒性,这是其在学习和记忆中的作用所必需的。因此,我们基于广泛的分岔分析的研究揭示了结构和生理参数在建立局部皮质网络基线工作状态中的功能优化和关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/baa2/11582336/88c31ae873ce/10827_2023_863_Fig1_HTML.jpg

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