Chemogenetic disruption of the hippocampus impairs gustatory preconditioning in rats

Adaptive behavior often relies on learning associations between stimuli that were never directly paired with reinforcement. Sensory preconditioning provides a powerful paradigm to investigate such indirect learning: when neutral stimuli A and X are paired during preconditioning, and X is subsequently paired with an unconditioned stimulus (US) during conditioning, stimulus A elicits conditioned response at test despite never being directly paired with the US. While the hippocampus is known to be critical for this process, its involvement in unimodal sensory preconditioning remains unclear. Here, we investigated the role of the hippocampus (dorsal and ventral) during different phases of gustatory preconditioning using chemogenetic approach in rats. We demonstrated that disruption of the hippocampus during either preconditioning or test selectively impaired the mediated aversion to A while leaving the direct conditioned aversion to X intact. These findings provide the first evidence that the hippocampus is necessary for unimodal gustatory preconditioning, extending previous demonstrations of hippocampal involvement in polymodal protocols. Our work therefore clarifies the critical role of the hippocampus in forming and retrieving purely gustatory associations to guide behavior, highlighting its function as a central hub for memory integration.