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

Functional abnormalities in the cerebellothalamic pathways in a mouse model of DYT25 dystonia

Dystonia is often associated with functional alterations in the cerebello-thalamic pathways, which have been proposed to contribute to the disorder by propagating pathological firing patterns to the forebrain. Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia. DYT25 (Gnal+/−) mice carry a heterozygous knockout mutation of the Gnal gene, which notably disrupts striatal function, and systemic or striatal administration of oxotremorine to these mice triggers dystonic symptoms. Our results reveal an increased cerebello-thalamic excitability in the presymptomatic state. Following the first dystonic episode, Gnal+/- mice in the asymptomatic state exhibit a further increase of the cerebello-thalamo-cortical excitability, which is maintained after θ-burst stimulations of the cerebellum. When administered in the symptomatic state induced by a cholinergic activation, these stimulations decreased the cerebello-thalamic excitability and reduced dystonic symptoms. In agreement with dystonia being a multiregional circuit disorder, our results suggest that the increased cerebello-thalamic excitability constitutes an early endophenotype, and that the cerebellum is a gateway for corrective therapies via the depression of cerebello-thalamic pathways.Fil: Aïssa, Hind Baba. Ecole Normale Supérieure; FranciaFil: Sala, Romain W.. Ecole Normale Supérieure; FranciaFil: Georgescu Margarint, Elena Laura. Ecole Normale Supérieure; FranciaFil: Frontera, Jimena Laura. Ecole Normale Supérieure; FranciaFil: Varani, Andrés Pablo. Ecole Normale Supérieure; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Menardy, Fabien. Ecole Normale Supérieure; FranciaFil: Pelosi, Assunta. Inserm; Francia. Université Pierre et Marie Curie; FranciaFil: Hervé, Denis. Université Pierre et Marie Curie; Francia. Inserm; Francia. Institut Du Fer À Moulin; FranciaFil: Léna, Clément. Ecole Normale Supérieure; FranciaFil: Popa, Daniela. Ecole Normale Supérieure; Franci

T-type channel blockade impairs long-term potentiation at the parallel fiber-Purkinje cell synapse and cerebellar learning

CaV3.1 T-type channels are abundant at the cerebellar synapse between parallel fibers and Purkinje cells where they contribute to synaptic depolarization. So far, no specific physiological function has been attributed to these channels neither as charge carriers nor more specifically as Ca 2+ carriers. Here we analyze their incidence on synaptic plasticity, motor behavior, and cerebellar motor learning, comparing WT animals and mice where T-type channel function has been abolished either by gene deletion or by acute pharmacological blockade. At the cellular level, we show that Ca V3.1 channels are required for long-term potentiation at parallel fiber-Purkinje cell synapses. Moreover, basal simple spike discharge of the Purkinje cell in KO mice is modified. Acute or chronic T-type current blockade results in impaired motor performance in particular when a good body balance is required. Because motor behavior integrates reflexes and past memories of learned behavior, this suggests impaired learning. Indeed, subjecting the KO mice to a vestibulo-ocular reflex phase reversal test reveals impaired cerebellum-dependent motor learning. These data identify a role of low-voltage activated calcium channels in synaptic plasticity and establish a role for CaV3.1 channels in cerebellar learning

: The influence of young researchers' career paths on mental health

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: The influence of young researchers' career paths on mental health

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S'appuyer sur un riche vivier de jeunes chercheur•ses dispersé•es

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LIBS analysis of agricultural soils: Accurate control of a portable LIBS instrument to assess the analytical ability of the method

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