Input-specific modulation of murine nucleus accumbens differentially regulates hedonic feeding

Daniel J. Christoffel, Jessica J. Walsh, Boris D. Heifets, Paul Hoerbelt, Sophie Neuner, Gordon Sun, Vinod K. Ravikumar, Hemmings Wu, Casey H. Halpern, Robert C. Malenka

Research output: Contribution to journalArticlepeer-review


Hedonic feeding is driven by the “pleasure” derived from consuming palatable food and occurs in the absence of metabolic need. It plays a critical role in the excessive feeding that underlies obesity. Compared to other pathological motivated behaviors, little is known about the neural circuit mechanisms mediating excessive hedonic feeding. Here, we show that modulation of prefrontal cortex (PFC) and anterior paraventricular thalamus (aPVT) excitatory inputs to the nucleus accumbens (NAc), a key node of reward circuitry, has opposing effects on high fat intake in mice. Prolonged high fat intake leads to input- and cell type-specific changes in synaptic strength. Modifying synaptic strength via plasticity protocols, either in an input-specific optogenetic or non-specific electrical manner, causes sustained changes in high fat intake. These results demonstrate that input-specific NAc circuit adaptations occur with repeated exposure to a potent natural reward and suggest that neuromodulatory interventions may be therapeutically useful for individuals with pathologic hedonic feeding.

Original languageEnglish (US)
Article number2135
JournalNature communications
Issue number1
StatePublished - Dec 1 2021

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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