Ion Channels and Disease Group, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.
Department of Neurology, Austin Health, Heidelberg, Australia.
PLoS Comput Biol. 2021 Oct 15;17(10):e1009521. doi: 10.1371/journal.pcbi.1009521. eCollection 2021 Oct.
Inhibitory interneurons shape the spiking characteristics and computational properties of cortical networks. Interneuron subtypes can precisely regulate cortical function but the roles of interneuron subtypes for promoting different regimes of cortical activity remains unclear. Therefore, we investigated the impact of fast spiking and non-fast spiking interneuron subtypes on cortical activity using a network model with connectivity and synaptic properties constrained by experimental data. We found that network properties were more sensitive to modulation of the fast spiking population, with reductions of fast spiking excitability generating strong spike correlations and network oscillations. Paradoxically, reduced fast spiking excitability produced a reduction of global excitation-inhibition balance and features of an inhibition stabilised network, in which firing rates were driven by the activity of excitatory neurons within the network. Further analysis revealed that the synaptic interactions and biophysical features associated with fast spiking interneurons, in particular their rapid intrinsic response properties and short synaptic latency, enabled this state transition by enhancing gain within the excitatory population. Therefore, fast spiking interneurons may be uniquely positioned to control the strength of recurrent excitatory connectivity and the transition to an inhibition stabilised regime. Overall, our results suggest that interneuron subtypes can exert selective control over excitatory gain allowing for differential modulation of global network state.
抑制性中间神经元塑造了皮质网络的脉冲特征和计算特性。中间神经元亚型可以精确地调节皮质功能,但中间神经元亚型促进皮质活动不同状态的作用仍不清楚。因此,我们使用连接和突触特性受实验数据约束的网络模型,研究了快速放电和非快速放电中间神经元亚型对皮质活动的影响。我们发现,网络特性对快速放电群体的调制更为敏感,降低快速放电兴奋性会产生强烈的尖峰相关性和网络振荡。矛盾的是,降低快速放电兴奋性会导致全局兴奋-抑制平衡的减少和抑制稳定网络的特征,其中网络的放电率由网络内兴奋性神经元的活动驱动。进一步的分析表明,与快速放电中间神经元相关的突触相互作用和生物物理特征,特别是它们快速的内在反应特性和短的突触潜伏期,通过增强兴奋性群体中的增益,使这种状态转变成为可能。因此,快速放电中间神经元可能具有独特的位置来控制递归兴奋性连接的强度和向抑制稳定状态的转变。总的来说,我们的结果表明,中间神经元亚型可以对兴奋性增益进行选择性控制,从而允许对全局网络状态进行差异调制。