Activation of a lateral hypothalamic-ventral tegmental circuit gates motivation

• Published in: PloS one 2019-07, Vol.14 (7), p.e0219522-e0219522
• Main Authors: Schiffino, Felipe L, Siemian, Justin N, Petrella, Michele, Laing, Brenton T, Sarsfield, Sarah, Borja, Cara B, Gajendiran, Anjali, Zuccoli, Maria Laura, Aponte, Yeka
• Format: Article
• Language: English
• Subjects: Activation; Addictive behaviors; Animals; Axon guidance; Behavior; Biology and Life Sciences; Brain; Brain research; Conditioning, Operant - physiology; Dopamine; Dopamine receptors; Drug abuse; Endocrinology; Feeding behavior; Feeding Behavior - psychology; Feeding methods; Female; Food; Food consumption; GABA; Gates (circuits); Gene expression; Gene therapy; Hypothalamic Area, Lateral - cytology; Hypothalamic Area, Lateral - physiology; Hypothalamus; Hypothalamus (lateral); Leptin; Luteinizing hormone; Male; Medicine and Health Sciences; Mice; Models, Animal; Modulators; Motivation; Motivation - physiology; Neural Pathways - physiology; Neuromodulation; Neurons; Neurons - physiology; Neuropeptides; Neurosciences; Physiological aspects; Public relations; Public relations executives; Reinforcement; Research and Analysis Methods; Reward; Rodents; Social Sciences; Society; Stereotaxic Techniques; Subpopulations; Synapses; Synaptogenesis; Ventral Tegmental Area - cytology; Ventral Tegmental Area - physiology; Ventral tegmentum; γ-Aminobutyric acid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0219522

Across species, motivated states such as food-seeking and consumption are essential for survival. The lateral hypothalamus (LH) is known to play a fundamental role in regulating feeding and reward-related behaviors. However, the contributions of neuronal subpopulations in the LH have not been thoroughly identified. Here we examine how lateral hypothalamic leptin receptor-expressing (LHLEPR) neurons, a subset of GABAergic cells, regulate motivation in mice. We find that LHLEPR neuronal activation significantly increases progressive ratio (PR) performance, while inhibition decreases responding. Moreover, we mapped LHLEPR axonal projections and demonstrated that they target the ventral tegmental area (VTA), form functional inhibitory synapses with non-dopaminergic VTA neurons, and their activation promotes motivation for food. Finally, we find that LHLEPR neurons also regulate 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.