Medial amygdala plasticity during pregnancy

Pregnancy is a period of extraordinary physiological plasticity, during which the female body prepares for the challenges of motherhood. Mounting evidence suggests that the brain, too, undergoes significant changes during this period. Human brain imaging studies have found that pregnancy is associated with stronger responses to infant stimuli, and many of these functional changes occur in brain areas that undergo structural remodelling during this period. It has been proposed that such changes promote robust parental attachment after parturition, but the underlying neural mechanisms are challenging to address in humans. Rodents are powerful models for studying the neural circuits underlying parental behaviour and understanding how hormones shape these circuits because (a) the main aspects of pregnancy are conserved between rodents and humans, (b) rodents display robust parental behaviour, and (c) the availability of advanced tools for deconstructing parenting circuits. While virgin female rodents typically avoid or attack pups, mothers are highly parental. Although the hormonal events of parturition were once thought to drive this behavioural switch, we recently demonstrated that it occurs during pregnancy in mice and relies on the remodelling of parenting-controlling neurons in the hypothalamus by hormones. A key observation was that these neurons receive more synaptic inputs during pregnancy, which convey pup-specific sensory information. This suggests that pregnancy alters how pup stimuli are perceived upstream of the hypothalamus. However, where and how such perceptual changes occur remains unknown. The medial amygdala (MeA) is a likely candidate: it directly projects to hypothalamic parenting-relevant neurons, processes chemosensory social stimuli, and is sensitive to pregnancy hormones. Classical studies in rats suggest that the MeA projects to both parenting- and avoidance-promoting centres in the hypothalamus. It was hypothesised that the relative strength of these projections influences whether animals nurture or avoid pups. We therefore hypothesise that pregnancy alters pup representations in the MeA, increasing stimulus selectivity and the response strength of pro-parental MeA projections, while decreasing the activity of avoidance-promoting projections. We propose that this shift in neural activity is critical for the onset of parental behaviour during pregnancy. This project will use viral-genetic circuit manipulations, behavioural assays, brain slice electrophysiology and in vivo calcium imaging to test this hypothesis. Elucidating the role of MeA plasticity during pregnancy will advance our understanding of how hormones affect sensory perception in the brain and how this contributes to behavioural changes. Pregnancy is increasingly recognised as a period of enormous brain plasticity – with key characteristics shared between humans and mice. A mechanistic understanding of how pregnancy hormones remodel brain circuits promises to advance our understanding of adaptive changes during this critical period. Importantly, such insights may also contribute to understanding the mechanisms underlying maladaptive changes, such as postpartum depression and anxiety.