PhD in neuroscience/physiopathology with a 3 years funding
Laboratory:
Institut de Neurobiologie de la Méditerranée (INMED)
INSERM UMR1249
Parc Scientifique de Luminy
BP 13
13273 Marseille Cedex 09- France
Team: “Early life imprinting and neurodevelopmental disorders”
Head of the team: Françoise Muscatelli
Contact: francoise.muscatelli@inserm.fr
Title: Oxytocin in early feeding behavior.
From birth, mammals have to find food to ensure growth and survival. Suckling must be initiated quickly after birth and then maintained and controlled. It is a complex process involving interactions
between sensory and motor neuronal pathways. The development of these circuits is disturbed in a variety of developmental disorders leading to long-term metabolic, behavioural and cognitive
dysfunctions. Interestingly, we showed in a genetic mouse model of a neurodevelopmental disorder, involving the MAGEL2 gene, that oxytocin is required to trigger the suckling activity.
· This project aims to understand the role of oxytocin in the suckling activity in normal mouse and pathological mouse models of neurodevelopmental diseases. We want to decipher the neuronal
circuitry and mechanism by which oxytocin activates the suckling initiation and maintenance. We will investigate the therapeutic action of oxytocin treatment on early feeding behavior.
· We will perform an integrative study and use behavioral, electrophysiological, cellular and functional neuroanatomical analyses to trace the neuronal circuit of suckling involving the oxytocin neurons, to decipher the action of oxytocin on motor pathways and to assess the therapeutic action of an early oxytocin treatment. We will conduct this project thanks to a panel of genetic and pharmacogenetic tools.
Our preliminary results and technical tools have shown the feasibility of this project. We expect to bring to light the important and not studied role of oxytocin in suckling activity and in the meantime to understand how suckling activity, is controlled. Today, this has been very poorly studied however it is a vital process that is altered in 80% of infants with neurodevelopmental disorders.
Key words: neurodevelopment, pathology, feeding, suckling, sucking.
Funding: a three-year funding is provided by a contract specific to the team and managed by INSERM.
References:
1-Bertoni A, Schaller F, Tyzio R, Gaillard S, Santini F, …Muscatelli F. (2021): Oxytocin administration in neonates shapes hippocampal circuitry and restores social behavior in a mouse model of autism. Mol Psychiatry. doi:10.1038/s41380-021-01227-
2-Muscatelli F and Bouret SG (2018): Wired for eating: how is an active feeding circuitry established in the postnatal brain? Current opinion in neurobiology. 52:165-171.doi:
10.1016/j.conb.2018.07.003
3-Muscatelli F, Desarmenien MG, Matarazzo V, Grinevich V (2018): Oxytocin Signaling in the Early Life of Mammals: Link to Neurodevelopmental Disorders Associated with ASD. Current topics in behavioral neurosciences. 35:239-268.doi: 10.7554/elife.32640
4-Tauber M, Boulanouar K, Diene G, Cabal-Berthoumieu S, Ehlinger V, Muscatelli F et al. (2017): The Use of Oxytocin to Improve Feeding and Social Skills in Infants With Prader-Willi Syndrome. Pediatrics. doi: 10.1542/peds.2016-2976
5-Meziane H, Schaller F, Bauer S, Villard C, Matarazzo V, …and Muscatelli F. (2015): 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. Biological psychiatry. 78: 85-94.
Candidate profile:
The candidate should be motivated by the topic, curious and interested to perform neurodevelopment studies in mouse models. Knowledge in physiology, neurodevelopment process, neuroanatomy is
required. Please send a CV with a motivation letter and names of two referees to francoise.muscatelli@inserm.fr