Biology subjects

Fortin-Houde, J.

Publications and source records attributed to Fortin-Houde, J..

4 recordsLinked to original sources

bioRxiv2026

Median raphe input to dorsal CA1 shapes VIP interneuron recruitment and novelty-guided spatial memory

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.

neuroscience↗

bioRxiv2026

Anatomical organization and origins of VGLUT3-positive axon terminals in the lateral septum.

The lateral septum (LS) integrates afferents from multiple brain regions, including the raphe nuclei. The organization of these inputs contributes to the regionalization of LS functions, for example spatial coding in dorsal LS and emotional regulation in ventral LS. Raphe-LS projections include glutamatergic axons expressing the vesicular glutamate transporter type 3 (VGLUT3), which often form pericellular baskets around LS neurons. This study provides an anatomical characterization of the organization and origins of VGLUT3-positive (VGLUT3+) raphe inputs to the LS. We mapped VGLUT3+ axon terminal density across the rostro-caudal extent of the LS and quantified colocalization with serotonin (5-HT) using immunohistochemistry. Our results showed that VGLUT3 density was highest in the ventral LS, whereas VGLUT3/5-HT colocalization was strongest in the dorsal LS. Retrograde viral vector-mediated tracing identified predominant inputs from the median raphe and B9 neuron group. Interestingly, the ventral hippocampus, a functionally related region which is known to also receive raphe VGLUT3 inputs, showed collaterals with the LS. Additional VGLUT3+ inputs to the LS arose from the interpeduncular nucleus, bed nucleus of the stria terminalis, nucleus incertus and pontine central gray. Anterograde tracing revealed that inputs from these brain regions target distinct and largely non-overlapping domains in the LS. Our findings highlight multiple sources of VGLUT3+ inputs to the LS, beyond the raphe nuclei, and suggest that distinct VGLUT3 circuits could contribute to LS functional specialization.

neuroscience↗

bioRxiv2025

Hyperexcitability of female serotonin neurons underlies sex-specific anxiety responses

Mood and anxiety disorders display robust sex differences in prevalence, symptom profile, and treatment outcomes, yet the circuit mechanisms underlying this sex bias remain unclear. Here, we identify a serotonergic (5-HT) pathway from the median raphe region (MRR) to the ventral hippocampus (vHP) that drives sex-specific anxiety regulation in mice. Using a multimodal approach combining electrophysiology, fiber photometry, and optogenetics, we show that vHP-projecting 5-HT neurons (5-HTvHP) in the MRR are intrinsically hyperexcitable in females and exhibit delayed adaptation during exposure to aversive environments. At baseline, female mice displayed greater avoidance and reduced risk-assessment behavior. Optogenetic activation of this pathway selectively enhanced anxiety-like behavior and stress-related grooming in females, while leaving locomotion unaffected. Fiber photometry revealed that grooming episodes coincide with transient suppression of 5-HTvHP activity, suggesting an adaptive feedback mechanism to downregulate serotonergic tone under elevated anxiety. Moreover, activation of this pathway disrupted hippocampal theta dynamics during habituation to a novel arena exclusively in females, revealing serotonergic modulation of anxiety and novelty processing. These results were consistent with the identification of sex-specific M-currents, which constrained excitability in male MRR 5-HTvHP neurons, while being largely absent in females. Collectively, our findings uncover a hyperexcitable MRR-vHP serotonergic circuit that drives female-specific anxiety states, providing a mechanistic framework for understanding sex-specific vulnerability to mood and anxiety disorders.

neuroscience↗

bioRxiv2022

Parallel streams of raphe VGLUT3-positive inputs target the dorsal and ventral hippocampus in each hemisphere.

The hippocampus (HP) receives neurochemically diverse inputs from the raphe nuclei, including glutamatergic fibers characterized by the expression of the vesicular glutamate transporter VGLUT3. These raphe-HP VGLUT3 (VGLUT3HP) projections have been suggested to play a critical role in HP functions, yet a complete anatomical overview of raphe VGLUT3 projections to the forebrain, and in particular the HP, is lacking. Using anterograde viral tracing, we describe largely non-overlapping VGLUT3-positive projections from the dorsal raphe (DR) and median raphe (MnR) to the forebrain, with the HP receiving inputs from the MnR. A limited subset of forebrain regions such as the amygdaloid complex, claustrum and hypothalamus receive projections from both the DR and MnR that remain largely segregated. This highly complementary anatomical pattern suggests contrasting roles for DR and MnR VGLUT3 neurons. To further analyse the topography of VGLUT3 raphe projections to the HP, we used retrograde tracing and found that VGLUT3HP neurons distribute over several raphe sub-regions (including the MnR, paramedian raphe and B9 nucleus) and lack co-expression of serotonergic markers. Strikingly, two-color retrograde tracing unraveled two parallel streams of VGLUT3-positive projections targeting the dorsal and ventral poles of the HP. These results demonstrate highly organized and segregated VGLUT3-positive projections to the HP, suggesting independent modulation of HP functions such as spatial memory and emotion-related behavior.

neuroscience↗