Venue : centre Broca
Anna SAINT-JEAN
Yves Le Feuvre
Cortical plasticity
Neurocentre Magendie
Title
Electrophysiologic, transcriptomic and morphologic plasticity of spinal GABAergic interneurons to decipher atypical mechanosensory perception in autism.
Abstract
Autism is characterized by impairments in social communication and interactions, as well as repetitive behaviours. Most people with autism also exhibit aberrant reactivity to sensory stimuli including tactile stimuli. In addition to being a major source of discomfort for autistic people, recent research suggests that tactile dysfunction may actually contribute to the development of the others core symptoms. This is why understanding the neural mechanisms behind tactile dysfunction is so important. Tactile information is perceived in the periphery and processed in the spinal cord under the control of inhibitory interneurons before being sent to higher brain structures. However, whether these inhibitory neurons undergo functional alterations in autistic models remain poorly understood. To explore the functional plasticity of spinal GABAergic interneurons (SGI) in autism, we used Fmr1-/y mice crossed with Gad1-GFP reporter lines. These mice exhibit haploinsufficiency for the Gad1 gene, which may interfere with the development of characteristic autistic phenotypes. We show that Fmr1-/y-Gad1-GFP mice display tactile deficits (longer latencies in tape removal test, decreased reactivity to brush stimulation), decreased anxiety in elevated plus maze, and social deficits, as typically observed in autistic models. Then, to characterize electrophysiologic, transcriptomic and morphologic properties of SGI in acute spinal slices we used the patch-seq technique. We observed that SGI exhibit altered excitability, characterized by an increased firing frequency of action potentials (AP) at low current injections, but a reduced frequency at high intensities compared to WT mice. This results in a narrower functional dynamic range, shifted toward lower-intensity stimulations. Importantly, transcriptomic analysis of recorded neurons reveals that these changes are restricted to a subpopulation of SGI expressing the parvalbumin (Pvalb) and the neuropeptide Y (NPY) marker. Altogether, we suggest that functional alterations of SGI, particularly Pvalb and NPY neurons in autism models may disrupt tactile information processing upstream of the brain and may play a critical role in the development of sensory
and social deficits characteristic of autism, underscoring their potential as therapeutic targets. Keywords Autism, spinal cord, GABAergic interneurons, patch-seq, electrophysiology, Fragile X Syndrome.
Jury
Mme Ingrid BUREAU, Chargée de Recherche, IBDM Marseille Rapportrice
Mr Eric LINGUEGLIA, Directeur de Recherche, IPMC Nice Rapporteur
Mr Alexandre FAVEREAUX, Professeur de l’Université de Bordeaux, IINS Bordeaux Examinateur
Mr Amaury FRANCOIS, Chargé de Recherche, IGF Montpellier Examinateur
Mme Graziella DI CRISTO, Professeure de l’Université de Montréal, CHU Sainte Justine Examinatrice
Mme Matilde CORDERO-ERAUSQUIN, Directrice de Recherche, INCI Strasbourg Examinatrice
Mr Yves LE FEUVRE, Chargé de Recherche, Neurocentre Magendie Bordeaux Directeur de thèse