In the hippocampal CA1 region, representations of past and present experience must be dynamically updated to support memory formation. This process depends on the integration of two major input pathways: contextual information from CA3 targeting proximal dendrites of pyramidal neurons, and sensory input from entorhinal cortex layer 3 (EC3) targeting distal dendrites. The relative contribution of these pathways is regulated by local inhibitory circuits, yet how these dynamics shape memory formation in vivo remains unclear. In particular, somatostatin-positive (SST) interneurons are positioned to gate these inputs through a combination of dendritic inhibition and disinhibition, suppressing distal EC3 inputs while also inhibiting cholecystokinin-positive (CCK) interneurons that provide feedforward inhibition onto CA3-driven proximal inputs. To investigate how these circuit mechanisms influence memory representations, we performed bidirectional chemogenetic manipulation of SST interneurons in mice during spatial and associative memory tasks, combining Fos-dependent Robust Activity Marker (F-RAM) labeling of engram cells with longitudinal 1-photon calcium imaging of CA1 pyramidal cell populations.
　Excitation of SST interneurons produced a marked increase in freezing during trace fear conditioning that persisted for at least one week, accompanied by an expansion of engram size in pyramidal cells. At the population level, SST excitation increased place cell turnover in both familiar linear track and novel trace fear environments, suggesting increased updating of hippocampal representations. In contrast, inhibition of SST interneurons reduced both freezing during trace fear conditioning and engram size relative to controls. In the familiar linear track environment, however, place field stability was enhanced and population activity was more highly correlated across sessions. To test how these changes in place field stability impact spatial coding, we performed an object location task in a highly familiar environment. SST excitation impaired object location discrimination, consistent with destabilization of the underlying spatial representation required for object encoding, whereas inhibition preserved discrimination. Taken together, these findings suggest that SST interneurons regulate the rate of representational updating in hippocampal CA1. We propose that SST-mediated inhibition of sensory EC3 inputs and disinhibition of CA3 contextual inputs provide a circuit-level mechanism that controls how rapidly CA1 representations shift during memory formation.