Role of oxytocin signalling in the development and function of hippocampal neurons

Oxytocin (Oxt) is a peptide hormone which is best known for its role in parturition and lactation. During the last decade, it has become clear that in addition Oxt can also participate in the regulation of brain development and in multiple brain processes, including cognition and social interactions. Detailed studies of clinical interest however into the role of Oxt during nerve cell differentiation and synaptogenesis have still not been carried out. This study investigates the role of Oxt signaling in the development and function of cultured murine hippocampal neurons. The results reported here show that Oxt exposure during the early stages of neuronal development exerts a priming role in the developing hippocampus by regulating the dendrite branching and the synapse formation of excitatory glutamatergic neurons but not inhibitory neurons, most likely due to the lack of the expression of the oxytocin receptors (Oxtrs) on inhibitory neurons. The manner in which Oxt can influence the central mechanisms of synaptogenesis implies that it may also play a role in the pathogenesis of neurobehavioural disorders. In particular, this work highlights how the constitutive deprivation of Oxt function in the Oxtr mouse model of autism offsets the excitatory (E)/inhibitory (I) synaptic balance toward an increased excitation in the hippocampal neuronal circuits, which may underlie the impaired social and cognitive functions exhibited by these mice. In conclusion, the results reported here indicate that Oxt input exerts an early priming role for the hippocampal development in vitro, regulating the balance between excitatory and inhibitory synapses and suggest that the lack of Oxt signaling may lead to neurobehavioural disturbances with an altered E/I ratio, such as autism and schizophrenia.