Stable, Variable, Encoding: Distinct Roles of SST, VIP, and EXC Neurons in Visual Novelty Processing

Detecting and processing novelty is critical for learning and survival, yet the stability and flexibility of novelty representations at the level of single neurons remain poorly understood. How novelty evoked responses persist across time, whether novel stimuli are encoded in a stimulus-specific or non-specific manner, and how encoding adapts under changing conditions remain largely unknown. Importantly, novelty responses involve both excitatory and inhibitory neurons, highlighting the need to understand how these cell types differentially contribute to stable and flexible cortical representations. We analyzed longitudinal calcium imaging dataset from mouse visual cortex, tracking excitatory (EXC), somatostatin-expressing (SST), and vasoactive intestinal peptide-expressing (VIP) neurons across six days of a change detection task incorporating contextual novelty, stimulus omissions, and absolute novelty. At the population level, novelty responses were stable across days. However, single-neuron analysis revealed marked instability in EXC and VIP neurons. SST neurons exhibited the highest single-cell stability across all conditions, suggesting a role in maintaining consistent sensory representations. VIP neurons displayed stable responses only to omissions. Regarding information content of novelty responses, we found that EXC neurons encoded both stimulus-specific and non-specific novelty while VIP neurons uniquely transitioned from non-specific to mixed encoding under absolute novelty, revealing previously unrecognized flexibility. These findings reveal distinct, cell-type-specific roles in novelty processing, with SST cells supporting stability and VIP cells adapting their coding to novelty type.