Gating of Social Behavior by Inhibitory Inputs from Hippocampal CA1 to Retrosplenial Agranular Cortex

Yuhan Shi; Jingjing Yan; Xiaohong Xu; Zilong Qiu

doi:10.1007/s12264-023-01172-0

Gating of Social Behavior by Inhibitory Inputs from Hippocampal CA1 to Retrosplenial Agranular Cortex

Neurosci Bull. 2024 Jan 28. doi: 10.1007/s12264-023-01172-0. Online ahead of print.

Authors

Yuhan Shi^{1

2}, Jingjing Yan², Xiaohong Xu², Zilong Qiu^{3

4

5

6}

Affiliations

¹ Songjiang Research Institute, Songjiang Hospital & MOE-Shanghai Key Laboratory for Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 201699, China.
² Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.
³ Songjiang Research Institute, Songjiang Hospital & MOE-Shanghai Key Laboratory for Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 201699, China. qiuzilong@shsmu.edu.cn.
⁴ Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China. qiuzilong@shsmu.edu.cn.
⁵ MOE-Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China. qiuzilong@shsmu.edu.cn.
⁶ Clinical Neuroscience Center, Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. qiuzilong@shsmu.edu.cn.

PMID: 38281278
DOI: 10.1007/s12264-023-01172-0

Abstract

The retrosplenial cortex has been implicated in processing sensory information and spatial learning, with abnormal neural activity reported in association with psychedelics and in mouse and non-human primate models of autism spectrum disorders (ASDs). The direct role of the retrosplenial cortex in regulating social behaviors remains unclear. In this work, we reveal that neural activity in the retrosplenial agranular cortex (RSA), a subregion of the retrosplenial cortex, is initially activated, then quickly suppressed upon social contact. This up-down phase of RSA neurons is crucial for normal social behaviors. Parvalbumin-positive GABAergic neurons in the hippocampal CA1 region were found to send inhibitory projections to the RSA. Blocking these CA1-RSA inhibitory inputs significantly impaired social behavior. Notably, enhancing the CA1-RSA inhibitory input rescued the social behavior defects in an ASD mouse model. This work suggests a neural mechanism for the salience processing of social behavior and identifies a potential target for ASD intervention using neural modulation approaches.

Keywords: Hippocampal CA1; Retrosplenial cortex; Social behavior.