Forebrain E-I balance controlled in cognition through coordinated inhibition and inhibitory transcriptome mechanism

Tian Tian; You Cai; Xin Qin; Jiangang Wang; Yali Wang; Xin Yang

doi:10.3389/fncel.2023.1114037

Forebrain E-I balance controlled in cognition through coordinated inhibition and inhibitory transcriptome mechanism

Front Cell Neurosci. 2023 Feb 24:17:1114037. doi: 10.3389/fncel.2023.1114037. eCollection 2023.

Authors

Tian Tian¹, You Cai^{1

2}, Xin Qin³, Jiangang Wang⁴, Yali Wang⁴, Xin Yang¹

Affiliations

¹ Shenzhen Key Laboratory of Translational Research for Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
² Department of Neurology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
³ Department of Medicine, Djavad Mowafaghian Centre for Brain Health, The University of British Columbia, Vancouver, BC, Canada.
⁴ Henan International Joint Laboratory of Non-Invasive Neuromodulation, Department of Physiology and Pathophysiology, Xinxiang Medical University, Xinxiang, China.

Abstract

Introduction: Forebrain neural networks are vital for cognitive functioning, and their excitatory-inhibitory (E-I) balance is governed by neural homeostasis. However, the homeostatic control strategies and transcriptomic mechanisms that maintain forebrain E-I balance and optimal cognition remain unclear.

Methods: We used patch-clamp and RNA sequencing to investigate the patterns of neural network homeostasis with suppressing forebrain excitatory neural activity and spatial training.

Results: We found that inhibitory transmission and receptor transcription were reduced in tamoxifen-inducible Kir2.1 conditional knock-in mice. In contrast, spatial training increased inhibitory synaptic connections and the transcription of inhibitory receptors.

Discussion: Our study provides significant evidence that inhibitory systems play a critical role in the homeostatic control of the E-I balance in the forebrain during cognitive training and E-I rebalance, and we have provided insights into multiple gene candidates for cognition-related homeostasis in the forebrain.

Keywords: E-I balance significance statement; GABA; cognition; forebrain; homeostasis.

Grants and funding

This study was supported by Shenzhen Science and Technology Program (Grant Nos. KQTD20210811090117032 and JCYJ20220530154409022); NSFC-Guangdong Joint Fund-U20A6005 (Grant No. ZDSYS20200828154800001); and Science and Technology Planning Project of Henan Province (212102310824).