Brain region-specific gain modulation of place cells by VIP neurons.

Gain modulation allows neurons to dynamically adjust their responsiveness to inputs without changing selectivity. While well-characterized in sensory areas, its role in higher-order brain regions governing spatial navigation and memory is unclear. Here, we used all-optical methods in mice performing a spatial task to demonstrate that vasoactive-intestinal peptide (VIP)-expressing neurons selectively control the gain of place cells and other cell types in the retrosplenial cortex (RSC) through disinhibition. Optogenetic manipulation revealed that this disinhibition, while broadly affecting network activity, selectively amplifies in-field place cell activity, improving spatial coding accuracy. In contrast, VIP neurons in the hippocampus have minimal impact on place field gain. Notably, simulations indicate that the benefit of gain modulation for RSC place cells is large compared to hippocampal place cells due to their much higher out-of-field activity and, therefore, lower signal-to-noise ratio. Here, we show an area-specific VIP-mediated gain control, enhancing spatial coding and, potentially, memory formation.