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Early life sensory dysfunction in mice lacking the autism-associated gene Magel2

o State of the art
Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits of social interaction and communication, as well as by repetitive interests and activities. However, atypical sensory behaviors are nowadays considered as a core aspect of ASD affecting 90 % of children and are observed well before the common symptoms. During the first week of life, sensory integrity is vital since neonates have to undertake innate behaviors such as nipple-searching and calls in response to sensory stimuli such as tactile contact, odor plumes with the mother, or reduction of the ambient temperature. Sensory depletion protocols during early life period demonstrate that sensory integration is detrimental for normal neurodevelopment and brain functions. Here we hypothesize that sensory dysfunctions at birth might cause some of the deficits observed later on in ASD patients.

o Objectives
Much of autism research in animal models of ASDs has focused on the social and cognitive difficulties and their underlying mechanisms. The aim of this project is to investigate early life sensory dysfunction using a mouse model of ASD well characterized in our lab. We have previously found sensory indifference during the first week of life. This deficit can be restored by pharmacological treatment with the neuropeptide Oxytocin. However, how this sensory circuitry is affected is unknown. The objectives of the project are to:
– Investigate the sensory circuitry from the periphery to central integration centers with focus on the facio-nasal sensory field, somatosensory cortex and preoptic area.
– Understand how oxytocin regulates early life sensory function.

o Methods
The project will use mouse ASD genetic model combined with neonatal behavioral testing, pharmacology and recording of cerebral activity in living neonate using electrophysiological and in vivo imaging techniques.
o Expected results
We expect to observed alteration in evoked potential that can be rescue by oxytocin or others agonist treatment.

o Expected candidate profile
o Candidat with knowledge and background in sensory information process, animal experiment, behavior, electrophysiology and in vivo recording experiment.

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References
1) Muscatelli, Desarmenien, Matarazzo & Grinevich. Oxytocin Signaling in the Early Life of Mammals: Link to Neurodéveloppemental Disorders Associated with ASD. Curr Top Behav Neurosci.;35:239-268. 2018
2) Necdin shapes serotonergic development and SERT activity modulating breathing in a mouse model for Prader-Willi syndrome. Elife; 31;6; 2017
3) Meziane et al. An Early Postnatal Oxytocin Treatment Prevents Social and Learning Deficits in Adult Mice Deficient for Magel2, a Gene Involved in Prader-Willi Syndrome and Autism ; Biol Psychiatry; 15;75(2):85-94. 2015

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