Median raphe input to dorsal CA1 shapes VIP interneuron recruitment and novelty-guided spatial memory
- 1Laval University
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.
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BibTeX
@misc{luo2026median,
title = {{Median raphe input to dorsal CA1 shapes VIP interneuron recruitment and novelty-guided spatial memory}},
author = {X. Luo and R. Radhakrishnan and A. Guet-McCreight and D. Topolnik and A. Bergeron and V. Dulam and L. D. Coulombe and M. Besner and J. Fortin-Houde and J. Davies and F. Michaud and B. Amilhon and L. Topolnik},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.752379},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752379v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Median raphe input to dorsal CA1 shapes VIP interneuron recruitment and novelty-guided spatial memory
AU - X. Luo
AU - R. Radhakrishnan
AU - A. Guet-McCreight
AU - D. Topolnik
AU - A. Bergeron
AU - V. Dulam
AU - L. D. Coulombe
AU - M. Besner
AU - J. Fortin-Houde
AU - J. Davies
AU - F. Michaud
AU - B. Amilhon
AU - L. Topolnik
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.752379
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.752379v1
AB - 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.
ER -