Pregnancy is associated with striking behavioral adaptations such as increased food intake, elevated aggressivity, and changes to infant-directed behavior. These changes are orchestrated by the action of pregnancy hormones on the brain, but the underlying mechanisms remain largely unknown.

Here we address how parenting circuits in mice are remodeled during pregnancy. We first establish that pregnancy affects specific aspects of infant-directed behavior. These adaptations are maximal in the last trimester and outlast the transient hormonal changes of pregnancy. Next, we quantify brain-wide, pregnancy-associated volumetric changes and ovarian hormone receptor expression to identify hormonally remodeled brain areas. These unbiased screens identify the medial preoptic area (MPOA) – a key node in parenting circuits – as a promising target. Indeed, deletion of ovarian hormone receptors in the MPOA abolishes pregnancy-associated behavioral adaptations. Strikingly, this is also the case when hormone receptors are selectively ablated in a small subset of parenting-relevant, Galanin-expressing MPOA neurons (MPOAGal neurons).

Using patch clamp recordings from acute brain slices, we surprisingly find that MPOAGal neurons undergo hormone-mediated silencing in late pregnancy. Microendoscopic calcium imaging in freely moving animals confirms that pregnancy profoundly reduces and decorrelates spontaneous MPOAGal activity. In addition, parenting-associated MPOAGal population activity is significantly sparsened in pregnancy, and pup representations segregate from representations of other social and non-social stimuli during this period, thereby increasing the discriminability of pup stimuli. This hormonally mediated adult plasticity is thus reminiscent of changes occurring during critical periods in the developing nervous system.

In summary, our work suggests that hormonal action remodels a small neuronal population to generate anticipatory behavioral changes during pregnancy.