Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward

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  • Al-Hasani, Ream
    • Other Affiliation: Washington University School of Medicine in St. Louis
  • McCall, Jordan G.
    • Other Affiliation: Washington University School of Medicine in St. Louis
  • Shin, Gunchul
    • Other Affiliation: University of Illinois at Urbana-Champaign
  • Gomez, Adrian M.
    • Other Affiliation: Washington University School of Medicine in St. Louis
  • Schmitz, Gavin P.
    • Other Affiliation: Washington University School of Medicine in St. Louis
  • Bernardi, Julio M.
    • Other Affiliation: Washington University School of Medicine in St. Louis
  • Pyo, Chang O.
    • Other Affiliation: University of Illinois at Urbana-Champaign
  • Park, Sung Il
    • Other Affiliation: University of Illinois at Urbana-Champaign
  • Marcinkiewcz, Catherine M.
    • School of Medicine
  • Crowley, Nicole A.
    • School of Medicine
  • Krashes, Michael J.
    • Other Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Lowell, Bradford B.
    • Other Affiliation: Harvard Medical School
  • Kash, Thomas L.
    • School of Medicine
  • Rogers, John A.
    • Other Affiliation: University of Illinois at Urbana-Champaign
  • Bruchas, Michael R.
    • Other Affiliation: Washington University School of Medicine in St. Louis
Abstract
  • The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photostimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and real-time aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and were positively reinforcing. These results show previously unknown discrete subregions of dynorphin-containing cells in the NAc shell that selectively drive opposing behaviors. Understanding the discrete regional specificity by which NAc dynorphinerigic cells regulate preference and aversion provides insight into motivated behaviors that are dysregulated in stress, reward, and psychiatric disease.
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  • Article
Rights statement
  • In Copyright
Journal title
  • Neuron
Journal volume
  • 87
Journal issue
  • 5
Language
  • English
ISSN
  • 1940-9567
  • 1097-4199
  • 0896-6273

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