Monaca, Francesco; (2025) The role of hormone-mediated neural remodelling in parental behaviour. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Understanding how physiological states shape information processing in neural circuits is a fundamental question in neuroscience. Parenting is an instinctive behaviour the onset of which is linked to pregnancy-related hormonal fluctuations. While dramatic progress has recently been made in dissecting the neural circuitry underlying parental behaviour, very little is known about the modulation of these circuits by the females reproductive state. This thesis proposes that pregnancy hormones remodel specific neurons in the hypothalamus to trigger changes in parental behaviour in mice. To examine how pregnancy-associated hormonal signals alter circuit function to promote parenting, parental behaviour was characterised during pregnancy. It was found that aspects of parental behaviour are changed during pregnancy and that these changes are most pronounced in late pregnancy. Most behavioural adaptations persisted until at least a month after pregnancy, indicating that they might result from long-lasting remodelling of the brain by pregnancy hormones. Ablation of receptors for ovarian hormones estradiol and progesterone from galanin-expressing MPOA (MPOA-Gal) neurons, a population critical for parenting, impaired parenting, showing that hormone action is required for pregnancy-induced behavioural changes. Electrophysiological recordings from these neurons in brain slices from virgin and pregnant females showed that, while estradiol silences MPOA-Gal neurons and increases their excitability, progesterone permanently rewires this circuit node by promoting dendritic spine formation and recruitment of excitatory synaptic inputs. Finally, in vivo endoscopic calcium imaging of MPOA-Gal population revealed that MPOA-Gal-specific neural remodelling sparsens population activity, resulting in stronger and more selective responses to pup stimuli. This work therefore demonstrates that the ovarian hormones estradiol and progesterone therefore act on MPOA-Gal neurons during pregnancy, thereby remodelling parenting circuits in preparation for motherhood.

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