Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning. 2017

Melissa J Sharpe, and Nathan J Marchant, and Leslie R Whitaker, and Christopher T Richie, and Yajun J Zhang, and Erin J Campbell, and Pyry P Koivula, and Julie C Necarsulmer, and Carlos Mejias-Aponte, and Marisela Morales, and James Pickel, and Jeffrey C Smith, and Yael Niv, and Yavin Shaham, and Brandon K Harvey, and Geoffrey Schoenbaum
National Institute on Drug Abuse, IRP, 251 Bayview Boulevard, Baltimore, MD 21228, USA; Princeton Neuroscience Institute, Princeton University, Washington Road, Princeton, NJ 08544, USA. Electronic address: melissa.sharpe@nih.gov.

Eating is a learned process. Our desires for specific foods 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 neurons in the 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 the storage of associative information about the cues leading to food in LH itself. Here, we present data 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 predicts food without affecting subsequent food consumption. In the second experiment, we show that this manipulation also disrupts the ability of 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.

UI MeSH Term Description Entries
D007026 Hypothalamic Area, Lateral Area in the hypothalamus bounded medially by the mammillothalamic tract and the anterior column of the FORNIX (BRAIN). The medial edge of the INTERNAL CAPSULE and the subthalamic region form its lateral boundary. It contains the lateral hypothalamic nucleus, tuberomammillary nucleus, lateral tuberal nuclei, and fibers of the MEDIAL FOREBRAIN BUNDLE. Lateral Hypothalamic Area,Lateral Hypothalamic Nucleus,Tuberomammillary Nucleus,Accessory Nucleus of the Ventral Horn,Area Hypothalamica Lateralis,Area Lateralis Hypothalami,Lateral Hypothalamus,Lateral Tuberal Nuclei,Lateral Tuberal Nucleus,Area Hypothalamica Laterali,Area Lateralis Hypothalamus,Area, Lateral Hypothalamic,Areas, Lateral Hypothalamic,Hypothalami, Area Lateralis,Hypothalamic Areas, Lateral,Hypothalamic Nucleus, Lateral,Hypothalamica Laterali, Area,Hypothalamica Lateralis, Area,Hypothalamus, Area Lateralis,Hypothalamus, Lateral,Lateral Hypothalamic Areas,Laterali, Area Hypothalamica,Lateralis Hypothalami, Area,Lateralis Hypothalamus, Area,Lateralis, Area Hypothalamica,Nuclei, Lateral Tuberal,Nucleus, Lateral Hypothalamic,Nucleus, Lateral Tuberal,Nucleus, Tuberomammillary,Tuberal Nuclei, Lateral,Tuberal Nucleus, Lateral
D007858 Learning Relatively permanent change in behavior that is the result of past experience or practice. The concept includes the acquisition of knowledge. Phenomenography
D008297 Male Males
D009042 Motivation Those factors which cause an organism to behave or act in either a goal-seeking or satisfying manner. They may be influenced by physiological drives or by external stimuli. Incentives,Disincentives,Expectations,Disincentive,Expectation,Incentive,Motivations
D003463 Cues Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. Cue
D005247 Feeding Behavior Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals. Dietary Habits,Eating Behavior,Faith-based Dietary Restrictions,Feeding Patterns,Feeding-Related Behavior,Food Habits,Diet Habits,Eating Habits,Behavior, Eating,Behavior, Feeding,Behavior, Feeding-Related,Behaviors, Eating,Behaviors, Feeding,Behaviors, Feeding-Related,Diet Habit,Dietary Habit,Dietary Restriction, Faith-based,Dietary Restrictions, Faith-based,Eating Behaviors,Eating Habit,Faith based Dietary Restrictions,Faith-based Dietary Restriction,Feeding Behaviors,Feeding Pattern,Feeding Related Behavior,Feeding-Related Behaviors,Food Habit,Habit, Diet,Habit, Dietary,Habit, Eating,Habit, Food,Habits, Diet,Pattern, Feeding,Patterns, Feeding,Restrictions, Faith-based Dietary
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012201 Reward An object or a situation that can serve to reinforce a response, to satisfy a motive, or to afford pleasure. Rewards
D017557 Ventral Tegmental Area A region in the MESENCEPHALON which is dorsomedial to the SUBSTANTIA NIGRA and ventral to the RED NUCLEUS. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the NUCLEUS ACCUMBENS. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of SCHIZOPHRENIA. Area Tegmentalis Ventralis,Ventral Tegmental Area of Tsai,Area Tegmentalis Ventrali,Tegmental Area, Ventral,Tegmentalis Ventrali, Area,Tegmentalis Ventralis, Area

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