UC Davis

Recent evidence suggests that some functions of the hippocampus (HPC) may be segregated along its transverse axis. For instance, the HPC receives spatial input from the medial entorhinal cortex (MEC) and postrhinal cortex, while it receives odor/object-related information from the lateral entorhinal cortex (LEC) and perirhinal cortex. Although these inputs are mixed in dentate gyrus and CA3, they remain segregated in the entorhinal cortex projections to CA1. The proximal (next to CA2) and distal (next to subiculum) segments of CA1 receive direct projections from MEC and LEC, respectively. This suggests that information processing may be functionally distinct along the proximo-distal axis of CA1. In our study, we examined how proximodistal segments of CA1 are involved in processing object-related information. First, we quantified c-Fos expression in proximal and distal CA1 of mice that were either exposed to a novel context, novel objects in a familiar context, or a familiar context without objects. Consistent with previous reports, we found that novel context exposure increased c-fos activity in proximal CA1 while exposure to novel objects resulted in higher c-fos levels in distal CA1 compared to control mice. Second, we examined the role of catecholamines in regulating activity of proximodistal CA1 neurons during object exploration. Catecholaminergic lesions in the hippocampus reduced c-Fos activity in both segments of CA1 and impaired performance of the hippocampal-dependent object location memory (OLM) task. Finally, we monitored calcium activity of proximodistal CA1 via fiber photometry while animals performed the OLM task. We observed differential activity in proximodistal CA1 during exploration of stationary and displaced objects. Overall, our results are consistent with the framework of the parallel circuits within the hippocampus; proximal CA1 is important for determining the animal’s location in space, while distal CA1 is involved in processing information about the content of an experience.