The activation of pBLA–vCA1 inputs remarkably increased approach behaviours and ameliorated anxiety and spatial memory deficits, while the simultaneous knockdown of Calb1 in vCA1 attenuated the beneficial effects of pBLA–vCA1 inputs both in wild-type and APP/PS1 mice, indicating the molecular mechanism of the pBLA–vCA1Calb1+ circuit. Here, APP is linked to Anxiety.