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选择性抑制兴奋性突触传递会改变神经网络的突发动力学。

Selective inhibition of excitatory synaptic transmission alters the emergent bursting dynamics of neural networks.

机构信息

Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.

Department of Neurology and Clinical Neurophysiology, St. Olav's University Hospital, Trondheim, Norway.

出版信息

Front Neural Circuits. 2023 Feb 16;17:1020487. doi: 10.3389/fncir.2023.1020487. eCollection 2023.

Abstract

Neurons connect to each other and form neural networks that display emergent electrophysiological activity. This activity begins as spontaneous uncorrelated firing in the early phase of development, and as functional excitatory and inhibitory synapses mature, the activity typically emerges as spontaneous network bursts. Network bursts are events of coordinated global activation among many neurons interspersed with periods of silencing and are important for synaptic plasticity, neural information processing, and network computation. While bursting is the consequence of balanced excitatory-inhibitory (E/I) interactions, the functional mechanisms underlying their evolution from physiological to potentially pathophysiological states, such as decreasing or increasing in synchrony, are still poorly understood. Synaptic activity, especially that related to maturity of E/I synaptic transmission, is known to strongly influence these processes. In this study, we used selective chemogenetic inhibition to target and disrupt excitatory synaptic transmission in neural networks to study functional response and recovery of spontaneous network bursts over time. We found that over time, inhibition resulted in increases in both network burstiness and synchrony. Our results indicate that the disruption in excitatory synaptic transmission during early network development likely affected inhibitory synaptic maturity which resulted in an overall decrease in network inhibition at later stages. These findings lend support to the importance of E/I balance in maintaining physiological bursting dynamics and, conceivably, information processing capacity in neural networks.

摘要

神经元相互连接,形成表现出涌现的电生理活动的神经网络。这种活动始于发育早期的自发无关联放电,随着功能性兴奋性和抑制性突触的成熟,活动通常表现为自发的网络爆发。网络爆发是许多神经元之间协调的全局激活事件,其间穿插着沉默期,对于突触可塑性、神经信息处理和网络计算非常重要。虽然爆发是平衡的兴奋-抑制(E/I)相互作用的结果,但它们从生理状态到潜在病理状态的进化的功能机制,例如同步性的增加或减少,仍然知之甚少。已知突触活动,特别是与 E/I 突触传递成熟相关的活动,强烈影响这些过程。在这项研究中,我们使用选择性化学遗传抑制来靶向和破坏神经网络中的兴奋性突触传递,以研究自发网络爆发的功能反应和恢复随时间的变化。我们发现,随着时间的推移,抑制导致网络爆发的突发性和同步性增加。我们的结果表明,早期网络发育过程中兴奋性突触传递的中断可能影响了抑制性突触的成熟,从而导致后期网络抑制整体下降。这些发现支持 E/I 平衡在维持生理爆发动力学以及可以想象的神经网络信息处理能力方面的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/509b/9978115/9fb1c888431b/fncir-17-1020487-g002.jpg

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