ИСТИНА

The hippocampus constructs cognitive maps by encoding spatial and self-motion-related information, crucial for flexible cognition and adaptive behavior. While CA1 neurons are key for spatial coding, their role in representing environmental features and behavioral states during spontaneous, reward-independent exploration remains unclear. Here, we investigated how hippocampal neurons encode place, objects, and behavior in a free-exploration task and how novelty decline across repeated exposures affects neuronal activity. We analyzed neuronal activity in C57Bl/6 mice freely exploring an open field (OF) for 10 minutes over 4 days. Behavioral analysis showed a progressive decrease in exploratory activity. To assess neuronal responses, we used c-Fos mapping and in vivo calcium imaging. First, we compared c-Fos expression between mice exposed to the OF once (high novelty) and 4 times (low novelty). c-Fos expression significantly decreased in the prefrontal and retrosplenial cortex with novelty reduction, whereas CA1 and CA3 expression remained unchanged. Second, we performed longitudinal miniscope calcium imaging of CA1 after AAV-mediated GCaMP6s expression and GRIN lens implantation. Over days, we tracked the activity of the same neurons and identified that ~10% of recorded cells functioned as place cells. Although the number of place cells remained stable across days, specific cells and their individual spatial selectivity changed over time, indicating an unstable spatial code. Additionally, we identified CA1 neurons selectively active during exploration of objects in the OF, specific behavioral acts (such as rearing, freezing, resting and running), and different OF zones (corners, walls, center). The proportion of neurons exhibiting such selectivity was relatively low (a few percent) and remained consistent across days. Our findings suggest that CA1 neurons encode not only spatial information but also objects in the OF as well as behavioral acts and states during free exploration. However, the instability of place cell selectivity across days indicates a dynamic spatial representation rather than a rigid map. Despite this dynamic coding, hippocampal reorganization was independent of novelty levels, suggesting that novelty detection relies on cortical rather than hippocampal circuits. These insights enhance our understanding of hippocampal processing during naturalistic behavior and may inform biologically inspired models of learning and memory. Supported by the Non-commercial Foundation for Support of Science and Education “INTELLECT”.