Deciphering the role of oxytocin in the cerebellum – CERBOT

Oxytocin is an evolutionary ancient neurohormone famous for its role in maternity and in attachment (“love hormone”). Recent studies point-out oxytocin as the hormone of “adaptation to the others”, i.e. , mainly, the social environment. Consequently, the central role of oxytocin and the physiology of the oxytocin system have been mainly studied in regions that belong to the “social brain”. Cerebellum was not, until recently, part of those brain circuits. However, in addition to its notorious contribution to motor control, the cerebellum has been recently shown to contribute to cognitive and emotional brain functions, and, in particular, to play an unexpected role in reward processing and social behavior adaptation. Moreover, as a major subcortical checkpoint connected to all the regions of the cerebral cortex, the cerebellum critically contributes to brain development. This could provide a causal substrate for the high incidence of autism-spectrum-disorders and learning disabilities in subjects with early cerebellar dysfunction or injuries.
We propose to study the oxytocin system (source, delivery mode and receptors) in the mouse cerebellum. Our preliminary results indicate the presence of oxytocin and its receptors in the cerebellum of developing and adult, male and female, mice. We observed oxytocin fibers and receptors in the deep nuclei and in the cortex of the cerebellum, in particular at the level of its principal integrative neurons, the Purkinje cells. The activity of those neurons appeared to be regulated by oxytocin..
To reach our goal, we have associated for this project experts in experimental physiology, neuroendocrinology, computational neuroscience and behavior.
The project consists of 3 work-packages designed and organized to: (1) study the origin of oxytocin and the location of its receptors in the cerebellum, (2) characterize its physiological effects on neuronal activity and integration of sensory inputs in the cerebellum, in vitro and in vivo, with electrophysiology and neuronal modeling, (3) investigate the contribution of the cerebellar oxytocin system to the adaptive behaviors, in particular social ones, and predictive function of the cerebellum.
The recent findings that oxytocin may treat some social communication deficits together with the increasing evidence that the cerebellum is a major contributor to neurodevelopmental conditions and to adaptive behaviors underline the importance of this research for the identification of new therapeutic targets.