Median raphe input to dorsal CA1 shapes VIP interneuron recruitment and novelty-guided spatial memory
Year: 2026
Type: preprint
Abstract: Vasoactive intestinal peptide–expressing interneurons (VIP-INs) gate hippocampal inhibition during novel experience, but the long-range signals that engage these cells remain poorly understood. Here we identify median raphe (MnR) projections as a brainstem pathway that tunes dorsal CA1 VIP-IN recruitment through coordinated glutamatergic and serotonergic mechanisms. Anatomical mapping and optogenetic recordings showed that MnR axons innervate multiple VIP-IN subtypes, while transcriptomic and pharmacological analyses revealed fast glutamatergic excitation together with serotonin receptor–dependent modulation of synaptic and intrinsic responsiveness. In vivo calcium imaging showed that novelty preferentially recruited a speed-coupled VIP-IN ensemble, and inhibition of MnR input selectively reduced the magnitude of this response. A hippocampal circuit model linked this pathway to dendritic disinhibition and place-cell recruitment. Behaviorally, inhibition of MnR input preserved exploratory engagement but disrupted the organization of spatial sampling and impaired object-location memory. Thus, MnR input organizes hippocampal disinhibition to support novelty-guided exploration and memory encoding.
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7213536516