Integrative neurohumoural regulation of oxytocin neurone activity in pregnancy and lactation

Abstract

Oxytocin is required for normal birth and lactation. Oxytocin is synthesised by hypothalamic supraoptic and paraventricular nuclei neurones and is released into the circulation from the posterior pituitary gland. Under basal conditions, circulating oxytocin levels are relatively constant but, during birth and lactation, pulsatile oxytocin release triggers rhythmic contraction of the uterus during birth and milk ejection during suckling. Oxytocin levels are principally determined by the pattern of action potential firing, which, in turn, is determined by the interplay between the intrinsic properties of the oxytocin neurones and the regulation of their excitability by surrounding glia, as well as by synaptic drive from their afferent inputs. During birth and suckling, oxytocin neurones fire high-frequency bursts of action potentials that are coordinated across the population of neurones. These bursts underpin the pulsatile secretion of oxytocin required for normal birth and lactation. Neuroglial regulation of oxytocin neurones changes during pregnancy to favour burst firing. However, these changes still require afferent input activity to drive activity. Although it has long been known that noradrenergic inputs to oxytocin neurones are activated during birth and lactation, the involvement of other afferent inputs is less clear. Here, we provide a brief overview of the current understanding of the mechanisms that regulate oxytocin neurone activity during pregnancy and lactation, and also focus on recent evidence from our laboratory identifying an input that increases kisspeptin production to excite oxytocin neurones in late pregnancy.