Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding

To understand hindbrain pathways involved in the control of food intake, we examined roles for calcitonin receptor (CALCR)-containing neurons in the NTS. Ablation of NTS Calcr abrogated the long-term suppression of food intake, but not aversive responses, by CALCR agonists. Similarly, activating Calcr(NTS) Ts neurons decreased food intake and body weight but (unlike neighboring Cck(NTS) cells) failed to promote aversion, revealing that Calcr(NTS) Ts neurons mediate a non-aversive suppression of food intake. While both Calcr(NTS) and Cck(NTS) neurons decreased feeding via projections to the PBN, Cck(NTS) cells activated aversive CGRP PM cells while Calcr(NTS) Ts cells activated distinct non-CGRP PBN cells. Hence, Calcr(NTS) Ts cells suppress feeding via non-aversive, non-CGRP PBN targets. Additionally, silencing Calcr(NTS) Ts cells blunted food intake suppression by gut peptides and nutrients, increasing food intake and promoting obesity. Hence, Calcr(NTS) Ts neurons define a hindbrain system that participates in physiological energy balance and suppresses food intake without activating aversive systems.