VIP interneurons control hippocampal place cell remapping through transient disinhibition in novel environments.

Abstract

Hippocampal place cells dynamically reorganize their activity, or "remap", to encode novel spatial environments, a process tightly regulated by inhibitory networks. Here, we identify vasoactive intestinal peptide (VIP)-expressing interneurons as key regulators of this plasticity. Using all-optical methods in mice navigating virtual reality, we show that novel environments trigger a transient increase in VIP interneuron activity, which facilitates rapid place field formation and stable spatial map construction. Bidirectional optogenetic manipulation --suppressing or upregulating VIP interneuron activity-- modulates the speed of spatial map formation and alters signatures of behavioral timescale plasticity (BTSP), a mechanism critical for place field induction. Both insufficient and excessive VIP interneuron activity impair reward-seeking behavior specifically in novel environments, revealing that a precise balance of VIP activity is essential for spatial learning. Our findings demonstrate that VIP interneurons gate a temporal window for place cell plasticity, mediating the impact of environmental novelty on hippocampal remapping and spatial memory.