An entorhinal-visual cortical circuit regulates depression-like behaviors.

Major depressive disorder is viewed as a 'circuitopathy'. The hippocampal-entorhinal network plays a pivotal role in regulation of depression, and its main sensory output, the visual cortex, is a promising target for stimulation therapy of depression. However, whether the entorhinal-visual cortical pathway mediates depression and the potential mechanism remains unknown. Here we report a cortical circuit linking entorhinal cortex layer Va neurons to the medial portion of secondary visual cortex (Ent→V2M) that bidirectionally regulates depression-like behaviors in mice. Analyses of brain-wide projections of Ent Va neurons and two-color retrograde tracing indicated that Ent Va→V2M projection neurons represented a unique population of neurons in Ent Va. Immunostaining of c-Fos revealed that activity in Ent Va neurons was decreased in mice under chronic social defeat stress (CSDS). Both chemogenetic inactivation of Ent→V2M projection neurons and optogenetic inactivation of the projection terminals induced social deficiency, anxiety- and despair-related behaviors in healthy mice. Chemogenetic inactivation of Ent→V2M projection neurons also aggravated these depression-like behaviors in CSDS-resilient mice. Optogenetic activation of Ent→V2M projection terminals rapidly ameliorated depression-like phenotypes. Optical recording using fiber photometry indicated that elevated neural activity in Ent→V2M projection terminals promoted antidepressant-like behaviors. Thus, the Ent→V2M circuit plays a crucial role in regulation of depression-like behaviors, and can function as a potential target for treating major depressive disorder. © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Citation

Jian Lu, Zhouzhou Zhang, Xinxin Yin, Yingjun Tang, Runan Ji, Han Chen, Yu Guang, Xue Gong, Yong He, Wei Zhou, Haiyang Wang, Ke Cheng, Yue Wang, Xiaowei Chen, Peng Xie, Zengcai V Guo. An entorhinal-visual cortical circuit regulates depression-like behaviors. Molecular psychiatry. 2022 Sep;27(9):3807-3820

Mesh Tags

PMID: 35388184

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