Sessions

The dorsomedial hypothalamic nucleus (DMH) plays a crucial role in terminating food intake by satiation. During pregnancy and lactation, mother animals exhibit hyperphagia as they must provide energy sources to their developing offspring. The neural regulatory pathways of this adaptation to lactation and the participating cell types have not been established yet. In the present study, we investigated the DMH as a potential regulatory centre for maternal adaptation.

We explored the inhibitory and excitatory afferent pathways of the DMH in transgenic mice with a fluorescent marker in the GABAergic neurons (VGAT-ZsGreen mouse line) by using a retrogradely transported neuronal tracer, cholera toxin beta subunit (CTB). Among the brain areas projecting to the DMH, we found regions involved in food intake control and maternal adaptation, such as the arcuate nucleus (Arc), in addition to the previously identified medial preoptic area (MPOA) and posterior intralaminar thalamic nucleus (PIL). This thalamic nucleus has been shown to receive suckling-related sensory cues from pups. Furthermore, the PIL neurons express a maternally induced neuropeptide, the parathyroid hormone 2 (PTH2), which has been suggested to play a role in facilitating milk production. Its potential involvement in maternal food intake is supported by its peak expression during the period of the most pronounced pup weight gain in the postpartum period.

By c-Fos immunolabeling, activation was found in the DMH of wild-type mother mice in response to pups. These activated neurons were further characterised by fluorescent immunolabeling, and a significantly higher density of GABAergic ZsGreen+ neurons was found in response to pups compared to mothers being separated from their pups. The activation pattern of PIL neurons was mapped in mother mice by CTB tract-tracing. We found that the DMH-projecting PIL neurons were activated in response to pups. We also revealed that a high proportion of PIL PTH2-expressing neurons project to the DMH. In addition to this, a prominent PTH2+ fibre network is located in the DMH, further supporting the anatomical interaction between the PIL PTH2+ and DMH neurons.

Fibre photometry in vivo calcium imaging measurements were carried out in VGAT-Cre mice following injection of an adeno-associated virus encoding the calcium sensor GCaMP8. During these measurements, GABAergic cells in the DMH were active during sniffing the food before eating.

The effect of maternally activated PIL neurons on food intake was investigated in TRAP2 mother mice by chemogenetically exciting PIL neurons that were previously active in response to pups, causing a strong tendency toward elevated food intake.

The findings suggest that DMH GABAergic neurons may be involved in the elevation of food intake in mothers, which is likely driven by DMH-projecting PTH2-expressing PIL neurons.