Lateral hypothalamic LEPR neurons drive appetitive but not consummatory behaviors
Justin N. Siemian,
Miguel A. Arenivar,
Sarah Sarsfield,
Cara B. Borja,
Charity N. Russell,
Yeka Aponte
Affiliations
Justin N. Siemian
Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224-6823, USA
Miguel A. Arenivar
Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224-6823, USA
Sarah Sarsfield
Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224-6823, USA
Cara B. Borja
Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224-6823, USA
Charity N. Russell
Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224-6823, USA
Yeka Aponte
Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, MD 21224-6823, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author
Summary: Assigning behavioral roles to genetically defined neurons within the lateral hypothalamus (LH) is an ongoing challenge. We demonstrate that a subpopulation of LH GABAergic neurons expressing leptin receptors (LHLEPR) specifically drives appetitive behaviors in mice. Ablation of LH GABAergic neurons (LHVGAT) decreases weight gain and food intake, whereas LHLEPR ablation does not. Appetitive learning in a Pavlovian conditioning paradigm is delayed in LHVGAT-ablated mice but prevented entirely in LHLEPR-ablated mice. Both LHVGAT and LHLEPR neurons bidirectionally modulate reward-related behaviors, but only LHVGAT neurons affect feeding. In the Pavlovian paradigm, only LHLEPR activity discriminates between conditioned cues. Optogenetic activation or inhibition of either population in this task disrupts discrimination. However, manipulations of LHLEPR→VTA projections evoke divergent effects on responding. Unlike food-oriented learning, chemogenetic inhibition of LHLEPR neurons does not alter cocaine-conditioned place preference but attenuates cocaine sensitization. Thus, LHLEPR neurons may specifically regulate appetitive behaviors toward non-drug reinforcers.
