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

作者：Huiling Yu, Liping Chen, Huiyang Lei, Guilin Pi, Rui Xiong, Tao Jiang, Dongqin Wu, Sun Fei, Yang Gao, Yuanhao Li, Wenju Peng, Bingyu Huang, Guoda Song, Xin Wang, Jingru Lv, Zetao Jin, Dan Ke, Ying Yang, Jian–Zhi Wang · 发表于：Nature Communications · 年份：2022 · DOI：10.1038/s41467-022-33139-6 · 被引用次数：47 · 研究领域：Neuroendocrine regulation and behavior、Stress Responses and Cortisol、Memory and Neural Mechanisms

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 pBLA Calb1 (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 pBLA Calb1 neuron activation. These findings suggest that the IL–pBLA Calb1 circuit could be a target to promote stress resilience via reward generalization and consequently ameliorate anxiety- and depression-like behaviours.