AGRP Neurons Project to the Medial Preoptic Area and Modulate Maternal Nest-Building

Abstract

AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP neurons also suppress competing actions and motivations to mediate adaptive behavioral selection during starvation. Here, in adult mice of both sexes we show that AGRP neurons form inhibitory synapses onto ϳ30% neurons in the medial preoptic area (mPOA), a region critical for maternal care. Remarkably, optogenetically stimulating AGRP neurons decreases maternal nest-building while minimally affecting pup retrieval, partly recapitulating suppression of maternal behaviors during food restriction. In parallel, optogenetically stimulating AGRP projections to the mPOA or to the paraventricular nucleus of hypothalamus but not to the LHA (lateral hypothalamus area) similarly decreases maternal nest-building. Chemogenetic inhibition of mPOA neurons that express Vgat (vesicular GABA transporter), the population targeted by AGRP terminals, also decreases maternal nest-building. In comparison, chemogenetic inhibition of neurons in the LHA that express vesicular glutamate transporter 2, another hypothalamic neuronal population critical for feeding and innate drives, is ineffective. Importantly, nest-building during low temperature thermal challenge is not affected by optogenetic stimulation of AGRP¡mPOA projections. Finally, via optogenetic activation and inhibition we show that distinctive subsets of mPOA Vgatϩ neurons likely underlie pup retrieval and maternal nest-building. Together, these results show that AGRP neurons can modulate maternal nest-building, in part through direct projections to the mPOA. This study corroborates other recent discoveries and underscores the broad functions that AGRP neurons play in antagonizing rivalry motivations to modulate behavioral outputs during hunger.

Sex differences in electrophysiological properties of mouse mPOA neurons revealed by in vitro whole-cell recordings

“…Single-cell RT-PCR were performed as previously described (Pfeffer et al, 2013, Li et al, 2019). Briefly, immediately after whole-cell formation, the contents of the neurons were aspirated into the patch electrode.…”

Hunger-Activated AgRP Neurons Inhibit MPOA Neurons Controlling Parenting

“…1). In addition, optogenetic stimulation of AgRP terminals in the MPOA in brain slices evoked IPSCs in ϳ30% of MPOA neurons in females and males (Li et al, 2019, their Fig. 2), indicating substantial functional connections between AgRP neurons and MPOA.…”

“…In a recent study, Li et al (2019) tested the hypothesis that AgRP neurons regulate parental care based on the feeding state of the parent by projecting to the MPOA. The authors first established that 25 h of food deprivation in multiparous females blunted some aspects of maternal care, namely active pup-oriented and non-pup-oriented behaviors, while leaving passive pup-oriented behaviors intact.…”

“…Hungry mothers also neglected nest building. But crouching over pups was unaffected (Li et al, 2019, their Table 1).…”

“…The authors next demonstrated that AgRP neurons are synaptically coupled with MPOA neurons and regulate some parental behaviors. First, a mouse line expressing the synaptic protein synaptophysin fused to tdTomato in AgRP neurons revealed the presence of synaptic terminals of AgRP neurons in the MPOA (Li et al, 2019, their Fig. 1).…”