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

Abstract

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.