A selective top-down pathway from anterior cingulate cortex embeds a representation of saliency in hippocampus

Abstract

For maximizing survival, animals must accurately memorize the structure of their environment. This is achieved by stabilizing and enriching hippocampal place cells near salient features, while the representation of neutral locations incrementally drifts with time. However, the circuit mechanisms by which top-down and bottom-up inputs selectively embed saliency into the hippocampal spatial map remain poorly understood. Here we identified a specific top-down input from the anterior cingulate cortex (ACC) to the dysgranular zone of the retrosplenial cortex (RSCd) that becomes active exclusively at reward locations. Activity of these ACC neurons is both necessary and sufficient for shaping the hippocampal saliency map. Unlike dopaminergic neurons in the ventral tegmental area, which respond to reward irrespective of the context, this class of ACC neurons encodes reward-context associations. Their optogenetic activation induces a reduction in locomotor speed, a behavioral correlate of saliency detection, while their inhibition disrupts the formation of the hippocampal place map. This work not only provides the first mechanistic insight into how context-dependent saliency is integrated in a top-down fashion into the hippocampal map to guide adaptive behavior but also challenges the classical view of memory consolidation theory where memory unidirectionally moves in bottom-up fashion from the hippocampus to the neocortex.