Fig. 7. Proposed working model.

a Heterogeneity in the BLA–vCA1 circuit under physiological conditions. The BLA shows proteomic diversity along its anterior–posterior axis at the molecular level. The anterior part of the BLA (aBLA) and the posterior BLA (pBLA) innervate the deep-layer calbindin1-negative neurons (Calb1−) and superficial-layer calbindin1-positive neurons (Calb1+) in vCA1, forming aBLA–vCA1 and pBLA–vCA1 circuits, respectively. This molecular and structural heterogeneity endows these pathways with functional heterogeneity in controlling approach-avoidance behaviour, i.e., the aBLA–vCA1^Calb1− circuit promotes avoidance and exerts an anxiogenic effect, while the pBLA–vCA1^Calb1+ circuit triggers approach and exerts an anxiolytic effect. b In AD, different protein network changes in response to Aβ deposition in the aBLA and pBLA impair the aBLA–vCA1^Calb1− and pBLA–vCA1^Calb1+ circuits. Together with their disorganised firing patterns, the AD mice prefer avoidance over approach in conflict tasks and display anxiety. Furthermore, Calb1 expression determines the anxiolytic effect of pBLA–vCA1^Calb1+ stimulation in AD, indicating a molecular mechanism at the exit node of the pBLA–vCA1^Calb1+ circuit.