Featured Paper of the Month – November 2019.
Motivated states such as food-seeking and consumption are essential for survival. A brain region called the lateral hypothalamus (LH) plays a fundamental role in regulating feeding and reward-related behaviors, but the contributions of specific neuronal subpopulations in the LH have not been thoroughly characterized. Here we examine how lateral hypothalamic leptin receptor-expressing (LHLEPR) neurons, a subset of GABAergic cells, regulate motivation in mice. We trained mice to lever-press for food pellets on a progressive ratio schedule, a model commonly used to assess motivation to obtain a reinforcer. We found that chemogenetic activation of LHLEPR neurons significantly increased progressive ratio (PR) responding, while inhibition decreased responding. We also mapped LHLEPR axonal projections and demonstrated that they target the ventral tegmental area (VTA) and form functional inhibitory synapses with non-dopaminergic VTA neurons. Optogenetic activation of this LHLEPR to VTA pathway also promoted motivation for food. Finally, we found that LHLEPR neurons additionally regulated motivation to obtain water, suggesting that they may play a generalized role in motivation. Together, these results identify LHLEPR neurons as modulators within a hypothalamic-ventral tegmental circuit that gates motivation.
PLoS One, 14 (7), pp. e0219522, 2019, ISSN: 1932-6203 (Electronic); 1932-6203 (Linking).