Identification of Critical Periods for the Neurodevelopmental and Behavioral Effects of Oxytocin

Funding Summary

This grant supports a new collaboration between two scientists with complimentary expertise. Drs. Sebastian Bouret and Francoise Muscatelli will work to define critical periods for oxytocin use in PWS models, and optimize this therapeutic approach. Mouse models will be used to define the critical period during which oxytocin might provide the maximum biological effect and impact.  The goal is to develop the optimal therapeutic strategy for oxytocin in PWS.  


Theresa Strong, Director of Research Programs, shares details on this project in this short video clip. 


Watch the full webinar describing the 11 research projects funded in this grant cycle here

Lay Abstract

Prader-Willi syndrome (PWS) is a genetic disorder characterized by an insatiable appetite and a variety of neurological and behavioral dysregulation. The hormone oxytocin is currently a promising topic in PWS research and treatment. Clinical trials have shown that oxytocin treatment can have lasting effects on appetite drive, social interactions and anxiety in patients with PWS, particularly if treatment is done in babies and infants. However, it is less clear whether such long-term beneficial health effects of oxytocin treatment can be seen in adult patients. We know that many key biological processes are established during the perinatal period —that time just prior to and soon after birth – and that alterations in biological systems can be reversed more persistently if intervention occurs during early life. The goal of this research project is to determine, using a pre-clinical mouse model for PWS, when do the maximal health and biological effects of oxytocin occur (birth, infancy, puberty, or adult life). It is also to better understand the neurological mechanisms by which oxytocin treatment exerts its effects on feeding and behavior in PWS. This research project promise to help developing optimal therapeutic strategies to ameliorate and hopefully permanently reverse feeding, neurological, and behavioral symptoms in PWS.

Research Outcomes: Public Summary

Clinical trials indicated that OT-based therapies in patients with PWS have positive effects on appetite drive and social interactions, particularly if treatment occurs during early life. However, it was less clear whether long-term beneficial effects can be seen in adult patients. There was, therefore, an important need to generate pre-clinical data in animal models to temporarily delineate closure of the critical period for OT action. There was also a need to better characterize the neurobiological and behavioral effects of OT therapies. The mouse genetic experiments of this project were designed to fill these knowledge gaps. We showed that the inactivation of OT neurons just after birth results in behavioral and neurodevelopmental dysregulations very much resembling those observed in a mouse model of PWS and SYS. We also found that the inactivation of OT neurons in later life (i.e., around puberty and adult life) can cause changes in behavior and metabolism, although more subtle than those found when chemogenetic inactivation of OT neurons occurred during early life. This basic science project was critical to determine the life period during which exogenous OT treatment might have a greater curative effect in SYS and PWS. Data derived from this project should help develop optimal therapeutic strategies to exert lasting beneficial effects on neurological and behavioral outcomes in patients with SYS and PWS.

Research Outcomes: Publications

Oxytocin administration in neonates shapes hippocampal circuitry and restores social behavior in a mouse model of autism. Bertoni A, Schaller F, Tyzio R,Gaillard S, Santini F, Xolin M, Diabira D, Vaidyanathan R, Matarazzo V, Medina I, Hammock E, Zhang J, Chini B, Gaiarsa J-L, Muscatelli F.  Molecular Psychiatry.

Funded Year:


Awarded to:

Sebastien Bouret and Francoise Muscatelli




Children's Hospital of Los Angeles and INSERM, France

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