Hypothalamic melanin concentrating hormone neurons communicate the nutrient value of sugar

Abstract

Sugars that contain glucose, such as sucrose, are generally preferred to artificial sweeteners owing to their post-ingestive rewarding effect, which elevates striatal dopamine (DA) release. While the post-ingestive rewarding effect, which artificial sweeteners do not have, signals the nutrient value of sugar and influences food preference, the neural circuitry that mediates the rewarding effect of glucose is unknown. In this study, we show that optogenetic activation of melanin-concentrating hormone (MCH) neurons during intake of the artificial sweetener sucralose increases striatal dopamine levels and inverts the normal preference for sucrose vs sucralose. Conversely, animals with ablation of MCH neurons no longer prefer sucrose to sucralose and show reduced striatal DA release upon sucrose ingestion. We further show that MCH neurons project to reward areas and are required for the post-ingestive rewarding effect of sucrose in sweet-blind Trpm5−/− mice. These studies identify an essential component of the neural pathways linking nutrient sensing and food reward.DOI: http://dx.doi.org/10.7554/eLife.01462.001

The role of dopamine in the pursuit of nutritional value

“…Stimulation of these neurons is shown to increase dopamine efflux in the striatum [39]. Importantly, while direct stimulation of dopamine neurons will generate a preference for water over sucrose [38], stimulation of MCH inputs does not generate a preference for water over sucrose [39]. Thus, the ability of MCH neurons to drive feeding and dopamine release seems dependent on a palatable taste input is required as well as neuronal activity.…”

“…The normal preference for sucrose (110-140 mM) over sucralose (0.5 mM) was reversed by pairing sucralose consumption with optogenetic stimulation of either dopamine neurons or a subset of inputs to dopamine neurons from melanin concentrating hormone (MCH)-expressing neurons of the lateral hypothalamus [38,39]. These neurons are excited by glucose via closure of ATP-gated potassium channels providing a mechanism by which changes in blood glucose could be rapidly relayed to the mesolimbic system [40].…”

“…These neurons are excited by glucose via closure of ATP-gated potassium channels providing a mechanism by which changes in blood glucose could be rapidly relayed to the mesolimbic system [40]. Stimulation of these neurons is shown to increase dopamine efflux in the striatum [39]. Importantly, while direct stimulation of dopamine neurons will generate a preference for water over sucrose [38], stimulation of MCH inputs does not generate a preference for water over sucrose [39].…”

“…For example, for stimulation of glucosesensitive MCH neurons to evoke dopamine efflux and induce feeding the presence of a taste input is required [39]. Observations that neutral cues associated with high ingestion of certain nutrients can drive learning and behaviour predicts the existence of neuroplasticity mechanisms that can induce alterations in subset of synapses in a highly specific manner.…”

“…Cre recombinase-expressing lines) provide a further ability to manipulate or record from neuronal populations that may encode the reinforcement value of nutrients [39].…”