Optogenetic Recruitment of Dorsal Raphe Serotonergic Neurons Acutely Decreases Mechanosensory Responsivity in Behaving Mice

The inhibition of sensory responsivity is considered a core serotonin function, yet this hypothesis lacks direct support due to methodological obstacles. We adapted an optogenetic approach to induce acute, robust and specific firing of dorsal raphe serotonergic neurons. In vitro, the responsiveness of individual dorsal raphe serotonergic neurons to trains of light pulses varied with frequency and intensity as well as between cells, and the photostimulation protocol was therefore adjusted to maximize their overall output rate. In vivo, the photoactivation of dorsal raphe serotonergic neurons gave rise to a prominent light-evoked field response that displayed some sensitivity to a 5-HT1A agonist, consistent with autoreceptor inhibition of raphe neurons. In behaving mice, the photostimulation of dorsal raphe serotonergic neurons produced a rapid and reversible decrease in the animals' responses to plantar stimulation, providing a new level of evidence that serotonin gates sensory-driven responses.ERC 250334, 5-HT OptogeneticMSCA 220098info:eu-repo/semantics/publishedVersio

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hM4Di experiment - mouse

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Fiber photometry experiment - mouse RIE (YFP control

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Fiber photometry experiment - mouse OH

Data from: Activity patterns of serotonin neurons underlying cognitive flexibility

Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty. Furthermore, by comparing the cue responses of serotonin and dopamine neurons, we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Our findings show how the activity patterns of serotonin neurons support a role in cognitive flexibility, and suggest a revised model of dopamine–serotonin opponency with potential clinical implications

Potentiel thérapeutique de la neuromodulation optogénétique

Apparues dans le courant des années 2000, les techniques de neuromodulation optogénétique ont considérablement accru notre pouvoir d’analyse du fonctionnement des systèmes nerveux en permettant l’utilisation d’impulsions lumineuses pour l’excitation et l’inhibition de populations neuronales ciblées génétiquement. Après avoir été adoptées de manière fulgurante par la communauté des neurosciences fondamentales, ces techniques sont aujourd’hui en passe d’ouvrir de nouvelles perspectives thérapeutiques. La neuromodulation optogénétique est un outil de choix pour l’étude de la physiopathologie de maladies neurologiques et neuropsychiatriques dans un certain nombre de modèles animaux. Elle pourrait ainsi accélérer la découverte de nouvelles stratégies thérapeutiques. De nouveaux traitements employant des protocoles de neuromodulation optogénétique pourraient également voir le jour à moyen terme, dans le but de traiter des maladies telles que l’épilepsie pharmaco-résistante et certains types de dégénérescences rétiniennes héréditaires, pour lesquelles il n’existe pas de solution thérapeutique satisfaisante

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Fiber photometry experiment - mouse POI (surprise outcome task

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hM4Di experiment - mouse

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Fiber photometry experiment - mouse LAG (surprise outcome task

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Fiber photometry experiment - mouse POI (TH-Cre mouse