ADAPTIVE SPATIAL CODING OF SOMATOSTATIN INTERNEURONS IN THE DENTATE GYRUS

The hippocampus plays a pivotal role in episodic memory formation. Within this structure, the dentate gyrus (DG) is essential for formation of novel and their discrimination from familiar memories. Although GABAergic inhibitory interneurons are increasingly recognized as key contributors to hippocampal computations as they control the timing and tuning of principal cell population activity, the mechanisms by which they contribute to memory formation remains still poorly understood. Here, we investigated the activity dynamics and information content of somatostatin-expressing interneurons (SOMIs) in the DG during novel context learning. Using two-photon calcium imaging, we recorded their activity across multiple days in head-fixed mice navigating through familiar and novel virtual environments performing a goal-oriented-learning task. Building on our previous work (Hainmueller, Cazala, et al., Nature Comm, 2024), we recorded the activity of two DG-SOMI subtypes that differ in their axonal distributions: hilar perforant-path-associated interneurons (HIPP) targeting distal apical principal cell dendrites in the molecular layer of the DG and SOMIs with axons in the hilus (HIL) presumably targeting hilar cells. We observed contrasting activity dynamics of both subtypes during novel context learning. HIPP axons exhibited high activity on the first few day of novelty exposure with a pronounced activity decline across days, whereas HIL axons exhibited reduced activity on the first days, which increased during familiarization. Together, these findings suggest SOM subtype-specific adaptations of their inhibitory output during contextual learning, which may contribute to experience-dependent routing of information from the entorhinal cortex through the DG to downstream hippocampal areas during memory formation.