Activation of basolateral amygdala to anterior cingulate cortex circuit alleviates MK-801 induced social and cognitive deficits of schizophrenia

Xin Huang; Yaohao Li; Haiying Liu; Jinwei Xu; Zehua Tan; Haoyang Dong; Biqing Tian; Shengxi Wu; Wenting Wang

doi:10.3389/fncel.2022.1070015

Activation of basolateral amygdala to anterior cingulate cortex circuit alleviates MK-801 induced social and cognitive deficits of schizophrenia

Front Cell Neurosci. 2022 Dec 22:16:1070015. doi: 10.3389/fncel.2022.1070015. eCollection 2022.

Authors

Xin Huang¹, Yaohao Li¹, Haiying Liu¹, Jinwei Xu¹, Zehua Tan¹, Haoyang Dong¹, Biqing Tian¹, Shengxi Wu¹, Wenting Wang¹

Affiliation

¹ Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi, China.

Abstract

Introduction: Schizophrenia is a severe psychiatric disorder with a high prevalence worldwide, however, its pathogenesis remains poorly understood.

Methods and results: In this study, we used the non-competitive NMDA receptor antagonist MK-801 to induce schizophrenia-like behaviors and confirmed that mice exhibited stereotypic rotational behavior and hyperlocomotion, social interaction defects and cognitive dysfunction, similar to the clinical symptoms in patients. Here, the anterior cingulate cortex (ACC) and basolateral amygdala (BLA) were involved in the schizophrenia-like behaviors induced by MK-801. Furthermore, we confirmed BLA sent glutamatergic projection to the ACC. Chemogenetic and optogenetic regulation of BLA-ACC projecting neurons affected social and cognitive deficits but not stereotypic rotational behavior in MK-801-treated mice.

Discussion: Overall, our study revealed that the BLA-ACC circuit plays a major role and may be a potential target for treating schizophrenia-related symptoms.

Keywords: MK-801; anterior cingulate cortex (ACC); basolateral amygdala (BLA); cognitive deficits; schizophrenia; social deficits; stereotypic rotational behavior.