vCA1 SST neurons represent avoidance states that guide anxiety-related behavioral choices

Abstract In uncertain, threatening environments, rapid and flexible behavioral decisions are essential for survival. The ventral CA1 region of the hippocampus encodes threatening contexts and can regulate avoidance-related behaviors. While activity patterns in excitatory neurons of vCA1 have been well characterized, the contributions of specific interneuron subtypes to avoidance decisions in threatening situations remain to be fully elucidated. Here, we show that somatostatin expressing (SST) interneurons in vCA1 are selectively recruited during avoidance behavior and play a causal role in shaping behavioral responses in aversive spaces. We find that vCA1 SST interneurons ramp their activity in anticipation of, and during, avoidance. This contrasted with parvalbumin (PV) and vasoactive intestinal peptide (VIP) interneurons, which are preferentially active during exploratory approach behaviors. Unlike other classes of vCA1 interneurons, SST neuron activity more reliably represented the animal’s intention to avoid rather than its spatial position. Moreover, optogenetic silencing of SST interneurons reduced the efficiency of approach-avoidance decisions. These findings identify vCA1 SST interneurons as key regulators of threat assessment, revealing a cell-type-specific mechanism by which vCA1 microcircuits govern avoidance behaviors. This work provides a new framework for understanding hippocampal control of avoidance behavior and highlights SST-expressing interneurons as key contributors to anxiety-related behaviors. Competing Interest Statement The authors have declared no competing interest.