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Hunger dampens a nucleus accumbens circuit to drive persistent food seeking.

Authors
  • Smith, Nicholas K1
  • Plotkin, Jared M2
  • Grueter, Brad A3
  • 1 Neuroscience Graduate Program, Vanderbilt University, Nashville, TN 37232, USA.
  • 2 College of Arts and Sciences, Vanderbilt University, Nashville, TN 37232, USA.
  • 3 Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, USA; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: [email protected]
Type
Published Article
Journal
Current biology : CB
Publication Date
Apr 25, 2022
Volume
32
Issue
8
Identifiers
DOI: 10.1016/j.cub.2022.02.034
PMID: 35259342
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To find food efficiently, a hungry animal engages in goal-directed behaviors that rely on nucleus accumbens (NAc) circuits. Synaptic alterations within these circuits underlie shifts in behavior across motivational states. Here, we show that hunger dampens an NAc to lateral hypothalamus (LH) circuit to promote persistent food seeking. BigLEN, a hunger-driven neuropeptide, acts through its receptor GPR171 to inhibit glutamate transmission onto NAc shell Drd1+ LH-projecting medium spiny neurons by suppressing cholinergic signaling. The antagonism of GPR171 in food-deprived animals reduces persistent unrewarded food-seeking behavior but does not alter effortful food seeking or overall food intake. The chemogenetic upregulation of the NAc to LH circuit reduces this persistent unrewarded responding in hungry animals. These results describe how hunger-driven neuromodulation targets a distinct dimension of motivated behavior by shaping information flow through anatomically defined circuit elements. Copyright © 2022 Elsevier Inc. All rights reserved.

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