Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning

Abstract

Eating is a learned process. Our desires for specificfoods arise through experience. Both electrical stimulation and optogenetic studies have shown that increased activity in the lateral hypothalamus (LH) promotes feeding. Current dogma is that these effects reflect a role for LH neuronsinthe control of the core motivation to feed, and their activity comes under control of forebrain regions to elicit learned food-motivated behaviors.However, these effects could also reflect thestorage of associative information about the cues leading to food in LH itself. Here, we presentdata from several studies that are consistent with a role for LH in learning. In the first experiment, we use a novel GAD-Cre rat to show that optogenetic inhibition of LH γ-aminobutyric acid (GABA) neurons restricted to cue presentation disrupts the rats' ability to learn that a cue predictsfood without affecting subsequent food consumption. In the second experiment, we showthat this manipulation also disrupts the abilityof a cue to promote food seeking after learning. Finally, we show that inhibition of the terminals of the LH GABA neurons in ventral-tegmental area (VTA) facilitates learning about reward-paired cues. These results suggest that the LH GABA neurons are critical for storing and later disseminating information about reward-predictive cues.