Infralimbic medial prefrontal cortex signalling to calbindin 1 positive neurons in posterior basolateral amygdala suppresses anxiety- and depression-like behaviours

Huiling Yu, Liping Chen, Huiyang Lei, Guilin Pi, Rui Xiong, Tao Jiang, Dongqin Wu, Fei Sun, Yang Gao, Yuanhao Li, Wenju Peng, Bingyu Huang, Guoda Song, Xin Wang, Jingru Lv, Zetao Jin, Dan Ke, Ying Yang () and Jian-Zhi Wang ()
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Huiling Yu: Huazhong University of Science and Technology
Liping Chen: Huazhong University of Science and Technology
Huiyang Lei: Huazhong University of Science and Technology
Guilin Pi: Huazhong University of Science and Technology
Rui Xiong: Huazhong University of Science and Technology
Tao Jiang: Huazhong University of Science and Technology
Dongqin Wu: Huazhong University of Science and Technology
Fei Sun: Huazhong University of Science and Technology
Yang Gao: Huazhong University of Science and Technology
Yuanhao Li: Huazhong University of Science and Technology
Wenju Peng: Huazhong University of Science and Technology
Bingyu Huang: Huazhong University of Science and Technology
Guoda Song: Huazhong University of Science and Technology
Xin Wang: Huazhong University of Science and Technology
Jingru Lv: Huazhong University of Science and Technology
Zetao Jin: Huazhong University of Science and Technology
Dan Ke: Huazhong University of Science and Technology
Ying Yang: Huazhong University of Science and Technology
Jian-Zhi Wang: Huazhong University of Science and Technology

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Generalization is a fundamental cognitive ability of organisms to deal with the uncertainty in real-world situations. Excessive fear generalization and impaired reward generalization are closely related to many psychiatric disorders. However, the neural circuit mechanism for reward generalization and its role in anxiety-like behaviours remain elusive. Here, we found a robust activation of calbindin 1-neurons (Calb 1) in the posterior basolateral amygdala (pBLA), simultaneous with reward generalization to an ambiguous cue after reward conditioning in mice. We identify the infralimbic medial prefrontal cortex (IL) to the pBLACalb1 (Calb 1 neurons in the pBLA) pathway as being involved in reward generalization for the ambiguity. Activating IL–pBLA inputs strengthens reward generalization and reduces chronic unpredictable mild stress-induced anxiety- and depression-like behaviours in a manner dependent on pBLACalb1 neuron activation. These findings suggest that the IL–pBLACalb1 circuit could be a target to promote stress resilience via reward generalization and consequently ameliorate anxiety- and depression-like behaviours.

Date: 2022
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DOI: 10.1038/s41467-022-33139-6

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