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The basolateral amygdala (BLA) and ventral hippocampal CA1 (vCA1) are cellularly and functionally diverse along their anterior–posterior and superficial-deep axes. Here, we find that anterior BLA (aBLA) and posterior BLA (pBLA) innervate deep-layer calbindin1-negative (Calb1−) and superficial-layer calbindin1-positive neurons (Calb1+) in vCA1, respectively. Photostimulation of pBLA–vCA1 inputs has an anxiolytic effect in mice, promoting approach behaviours during conflict exploratory tasks. By contrast, stimulating aBLA–vCA1 inputs induces anxiety-like behaviour resulting in fewer approaches. During conflict stages of the elevated plus maze task vCA1 Calb1+  neurons are preferentially activated at the open-to-closed arm transition, and photostimulation of vCA1 Calb1+  neurons at decision-making zones promotes approach with fewer retreats. In the APP/PS1 mouse model of Alzheimer’s disease, which shows anxiety-like behaviour, photostimulating the pBLA–vCA1 Calb1+  circuit ameliorates the anxiety in a Calb1-dependent manner. These findings suggest the pBLA–vCA1 Calb1+  circuit from heterogeneous BLA–vCA1 connections drives approach behaviour to reduce anxiety-like behaviour.

Posterior basolateral amygdala to ventral hippocampal CA1 drives approach behaviour to exert an anxiolytic effect