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Lateral hypothalamic LEPR neurons drive appetitive but not consummatory behaviors

Justin Siemian, Ph.D.

Justin Siemian, Ph.D.

Featured Paper of the Month – April 2022

Published in Cell Reports by Justin Siemian and Yeka Aponte, et al. of the NIDA IRP Neuronal Circuits and Behavior Unit.

Summary

The lateral hypothalamus (LH) has long been known for its involvement in feeding behaviors. Specifically, GABAergic LH (LHVGAT) neurons are known to mediate food intake (consummatory) and food-seeking (appetitive) behaviors, but GABAergic neurons comprise a large population of neurons that can further be divided into genetically identified subpopulations. Therefore, we sought to determine the function of a subset of LHVGAT neurons identified as leptin receptor-expressing neurons (LHLEPR neurons). We used a combination of neuronal ablation, optogenetics, chemogenetics, and in vivo calcium imaging to study the contributions of LHLEPR neurons to the greater LHVGAT population in mice. We found that while the broader LHVGAT population is involved in appetitive, consummatory and anxiety-like/displacement behaviors, LHLEPR neurons are responsible for driving appetitive behaviors. Our study highlights the need for continued dissection of neuronal subpopulations and their behavioral contributions to feeding behaviors.

Publication Information

Siemian, Justin N; Arenivar, Miguel A; Sarsfield, Sarah; Borja, Cara B; Russell, Charity N; Aponte, Yeka

Lateral hypothalamic LEPR neurons drive appetitive but not consummatory behaviors Journal Article

In: Cell Rep, vol. 36, no. 8, pp. 109615, 2021, ISSN: 2211-1247.

Abstract | Links

@article{pmid34433027b,
title = {Lateral hypothalamic LEPR neurons drive appetitive but not consummatory behaviors},
author = {Justin N Siemian and Miguel A Arenivar and Sarah Sarsfield and Cara B Borja and Charity N Russell and Yeka Aponte},
url = {https://pubmed.ncbi.nlm.nih.gov/34433027/},
doi = {10.1016/j.celrep.2021.109615},
issn = {2211-1247},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Cell Rep},
volume = {36},
number = {8},
pages = {109615},
abstract = {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 (LH) specifically drives appetitive behaviors in mice. Ablation of LH GABAergic neurons (LH) decreases weight gain and food intake, whereas LH ablation does not. Appetitive learning in a Pavlovian conditioning paradigm is delayed in LH-ablated mice but prevented entirely in LH-ablated mice. Both LH and LH neurons bidirectionally modulate reward-related behaviors, but only LH neurons affect feeding. In the Pavlovian paradigm, only LH activity discriminates between conditioned cues. Optogenetic activation or inhibition of either population in this task disrupts discrimination. However, manipulations of LH→VTA projections evoke divergent effects on responding. Unlike food-oriented learning, chemogenetic inhibition of LH neurons does not alter cocaine-conditioned place preference but attenuates cocaine sensitization. Thus, LH neurons may specifically regulate appetitive behaviors toward non-drug reinforcers.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

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 (LH) specifically drives appetitive behaviors in mice. Ablation of LH GABAergic neurons (LH) decreases weight gain and food intake, whereas LH ablation does not. Appetitive learning in a Pavlovian conditioning paradigm is delayed in LH-ablated mice but prevented entirely in LH-ablated mice. Both LH and LH neurons bidirectionally modulate reward-related behaviors, but only LH neurons affect feeding. In the Pavlovian paradigm, only LH activity discriminates between conditioned cues. Optogenetic activation or inhibition of either population in this task disrupts discrimination. However, manipulations of LH→VTA projections evoke divergent effects on responding. Unlike food-oriented learning, chemogenetic inhibition of LH neurons does not alter cocaine-conditioned place preference but attenuates cocaine sensitization. Thus, LH neurons may specifically regulate appetitive behaviors toward non-drug reinforcers.

Close

  • https://pubmed.ncbi.nlm.nih.gov/34433027/
  • doi:10.1016/j.celrep.2021.109615

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