OXYTOCINERGIC SYSTEM AND SUCKLING BEHAVIOR IN MICE NEWBORNS

Suckling is a vital mammalian behavior triggered by maternal sensory cues. Suckling impairment is a common symptom in many neurodevelopmental disorders, such as Prader-Willi (PW) and Schaaf-Yang (SY) syndromes, requiring nasogastric tube feeding at birth. Both syndromes are associated with mutations in the MAGEL2 gene, an imprinted paternally expressed gene. Our preclinical studies, on Magel2-deficient mouse model (Magel2 KO), revealed suckling impairment in mutant newborns associated with an oxytocinergic system deficiency and restored by oxytocin (OT) treatment. Our hypothesis is that maternal care stimulates OT neurons, which in turn modulate the sensory and motor nuclei activity involved in the initiation of suckling; in Magel2 KO pups, this neuronal circuit may be dysfunctional. In control and mutant newborn mice, we have 1) mapped and quantified, via cFos immunolabeling, the activity of brain regions at birth, during first maternal care and during first suckling focusing on the OT system 2) characterized and evaluated, via a nipple grasping test, the pup’s suckling behavioral sequence.This study reveals two OT neuron subpopulations activated either during maternal care or sucking in control mice and an impaired activity in mutants. In mutants, maternal care differentially activates brainstem sensory and motor nuclei involved in suckling and the nipple grasping test, just aftre birth, shows an impairment of the sucking motor activity. This study will shed light on brain regions activated in suckling and OT neurons involvement. Understanding these processes will allow us to propose optimal oxytocin-based treatments for babies with PW, SY, or other neurodevelopmental disorders.