Dorsal hippocampus mediates light–tone associations in male mice

Daily choices are often influenced by environmental cues that are not directly associated with reinforcers. This phenomenon, known as higher-order conditioning, can be studied using sensory preconditioning tasks in rodents. This behavioral paradigm involves the repeated pairing of two innocuous stimuli, such as a light and a tone, followed by a devaluation phase in which one stimulus is associated with an unconditioned stimulus, such as a mild footshock. The result is a conditioned response (e.g., freezing) to both the conditioned stimulus (direct learning) and the non-conditioned stimulus (mediated learning). In our study, we successfully established a light-tone sensory preconditioning task specifically in male mice, as sex differences were observed in both control experimental groups and in sensory preconditioning responses. We employed in vivo, freely moving fiber photometry to monitor neural activity in the dorsal and ventral subregions of the hippocampus in male mice during the formation of associations between innocuous stimuli and reinforcers. Additionally, we combined our sensory preconditioning task with chemogenetic approaches to investigate the roles of these hippocampal subregions in sensory preconditioning. Our results indicate that dorsal, but not ventral, CaMKII-positive neurons are involved in encoding innocuous stimuli during the preconditioning phase. Overall, we developed a novel light-tone sensory preconditioning protocol in male mice, enabling the detection of sex differences and furthering our understanding of how specific hippocampal subregions and cell types regulate complex cognitive processes.