PrOMClactin · Prolactin-guided remodelling of POMC neurons circuitry and function during female reproductive states

Pregnancy and lactation involve deep hormonal fluctuations that drive maternal behaviours and reshape the neuroplastic female brain. While much is known about classical maternal caregiving circuits, how neural networks beyond these regions are reshaped to support the broader physiological and behavioural demands of motherhood, is poorly understood. The arcuate nucleus of the hypothalamus (ARC), a key integrator of hormonal and metabolic signals, is ideally positioned to mediate such adaptations. Yet, the extent and nature of ARC neuronal remodelling during female reproductive states (FRS) are largely unknown. Preliminary data from my host laboratory reveal that FRS induce dynamic neuroplasticity within the ARC. Specifically, POMC neurons show marked and state-dependent expression of the reproductive hormone prolactin receptor (PrlR). The expression levels of this receptors and the proportion of PrlR-expressing POMC neurons (POMCPrlR) fluctuate across FRS. Furthermore, a subset of POMC is activated upon suckling and the ablation of those neurons in females lads to lack of maternal care and death of the offspring. These findings suggest that POMC neurons are uniquely responsive to the maternal hormonal milieu and may orchestrate critical behavioural and physiological adaptations during motherhood. This project aims to unravel the role and reconfiguration of neurons in meeting the allostatic demands of reproduction. Drawing on my expertise in neuroendocrinology and hypothalamic function, and employing cutting-edge molecular and behavioural tools, I will (1) dissect the role of prolactin receptor in POMC neurons, (2) define the plastic functional microarchitecture of POMCPrlR neurons and (3) decipher the identity, function, and neuroadaptive mechanisms of postsynaptic targets of POMCPrlR neurons during FRS. This work will provide unprecedented insights into female-specific brain plasticity beyond caregiving circuits, redefining our understanding of the maternal brain.