Multiple NTS neuron populations cumulatively suppress food intake

Several discrete groups of feeding-regulated neurons in the nucleus of the solitary tract (nucleus tractus solitarius; NTS) suppress food intake, including avoidance-promoting neurons that express Cck (NTS^Cck cells) and distinct Lepr- and Calcr-expressing neurons (NTS^Lepr and NTS^Calcr cells, respectively) that suppress food intake without promoting avoidance. To test potential synergies among these cell groups, we manipulated multiple NTS cell populations simultaneously. We found that activating multiple sets of NTS neurons (e.g. NTS^Lepr plus NTS^Calcr [NTS^LC], or NTS^LC plus NTS^Cck [NTS^LCK]) suppressed feeding more robustly than activating single populations. While activating groups of cells that include NTS^Cck neurons promoted conditioned taste avoidance (CTA), NTS^LC activation produced no CTA despite abrogating feeding. Thus, the ability to promote CTA formation represents a dominant effect but activating multiple non-aversive populations augments the suppression of food intake without provoking avoidance. Furthermore, silencing multiple NTS neuron groups augmented food intake and body weight to a greater extent than silencing single populations, consistent with the notion that each of these NTS neuron populations plays crucial and cumulative roles in the control of energy balance. We found that silencing NTS^LCK neurons failed to blunt the weight-loss response to vertical sleeve gastrectomy (VSG) and that feeding activated many non-NTS^LCK neurons, however, suggesting that as-yet undefined NTS cell types must make additional contributions to the restraint of feeding.