Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward.
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 was 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.
Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: alhasanir@morpheus.wustl.edu.
Ream
R
Al-Hasani
Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Jordan G
JG
McCall
Department of Materials Science and Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Gunchul
G
Shin
Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Adrian M
AM
Gomez
Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Gavin P
GP
Schmitz
Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Julio M
JM
Bernardi
Department of Electrical and Computer Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Chang-O
CO
Pyo
Department of Materials Science and Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Sung Il
SI
Park
Department of Pharmacology and Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27516, USA.
Catherine M
CM
Marcinkiewcz
Department of Pharmacology and Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27516, USA.
Nicole A
NA
Crowley
Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA; Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Michael J
MJ
Krashes
Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Bradford B
BB
Lowell
Department of Pharmacology and Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27516, USA.
Thomas L
TL
Kash
Department of Materials Science and Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Electrical and Computer Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
John A
JA
Rogers
Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: bruchasm@wustl.edu.
Michael R
MR
Bruchas
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D003216:Conditioning, Operant; D004399:Dynorphins / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000145:classification / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology*; D010775:Photic Stimulation; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D012201:Reward; D012653:Self Stimulation; D013997:Time Factors; D059015:Wireless Technology
C000600618:DRD2 protein, mouse; D008164:Luminescent Proteins; D011498:Protein Precursors; D017448:Receptors, Dopamine D2; C036448:pre-prodynorphin; D004399:Dynorphins