Brain Region-specific Gain Modulation of Place Cells by VIP Neurons

Gain modulation allows neurons to dynamically adjust their responsiveness to sensory inputs without changing selectivity. While this process is well-characterized in sensory areas, its role in higher-order brain regions, like those 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 fields in the retrosplenial cortex (RSC) through disinhibition. Optogenetic manipulation revealed that this disinhibition selectively amplifies in-field 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 exceptionally large compared to hippocampal place cells due to their much higher out-of-field activity and, therefore, lower signal-to-noise ratio. These findings reveal an area-specific specialization of VIP-mediated gain control, enhancing spatial coding and, potentially, the formation of new spatial memories.