# Control of CA2 by its cortico-hippocampal inputs and local inhibition in social information processing and learning > **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $587,549 ## Abstract PROJECT SUMMARY The neural mechanisms by which the hippocampus encodes social memory, the ability to recognize and recall encounters with a conspecific, remain largely unexplored. As social dysfunction and social memory impairment are associated with a number of neuropsychiatric disorders, a deeper understanding of the neural bases of social memory is needed to enhance our understanding of disease mechanisms. Here, we focus on the hippocampal CA2 region, as CA2 pyramidal neurons have recently been found to play a central role in social memory in mice. Moreover, CA2 abnormalities have been identified in several human diseases and their mouse models. Although progress has been made in defining the role of CA2 in a simple form of social memory—the ability of a mouse to distinguish a novel from a familiar individual—a number of fundamental questions remain. What social sensory information is encoded in CA2? How is social information relayed to CA2 through its cortical-hippocampal inputs? Does CA2 participate in forms of social memory more complex than social familiarity? Here we address such questions by examining neural representations of the most salient social cue for mice, mouse urine, and how those representations are modified by odor-reward learning. We use 2-photon calcium imaging in head-fixed mice to assess CA2 neuron responses to social and non-social odors in an odor-reward learning paradigm in which a mouse is trained to associate one of two odors with a water reward. We find that social-odor reward learning both requires CA2 and enhances the ability of CA2 pyramidal neuron activity to distinguish between rewarded and unrewarded social odors. Although CA2 also distinguishes non- social odors, non-social odor learning neither requires CA2 nor enhances CA2 non-social odor discrimination. Thus, CA2 is specialized for the encoding of associations between a social stimulus and reward, and this encoding is behaviorally relevant. Here we ask how social information is delivered to CA2 and whether odor classification and odor- reward learning are computed locally in CA2 or inherited from CA2 inputs. We will address these questions using optogenetic inhibition of the three major cortico-hippocampal inputs to CA2: entorhinal cortex, dentate gyrus, and CA3. We will perform two-photon calcium imaging from these regions to examine and compare their representations of social and non-social odors, before and after odor-reward learning, with our results in CA2. Finally, we will use optogenetics and two photon imaging to characterize the odor representations and role in odor learning of three distinct populations of CA2 inhibitory neurons that have been implicated in social memory. Through this comprehensive analysis, we aim to provide the first detailed examination of how social odors and odor-reward learning is processed through the cortico-hippocampal circuit to allow socially-relevant experiences to be incorporated into social memory representations... ## Key facts - **NIH application ID:** 10803620 - **Project number:** 2R01MH104602-11 - **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES - **Principal Investigator:** STEVEN A SIEGELBAUM - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $587,549 - **Award type:** 2 - **Project period:** 2014-07-11 → 2028-10-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10803620 ## Citation > US National Institutes of Health, RePORTER application 10803620, Control of CA2 by its cortico-hippocampal inputs and local inhibition in social information processing and learning (2R01MH104602-11). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10803620. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*