title: Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity.
abstract: Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic KOR inhibition decreases the excitatory drive of D1 MSN activity by the amygdala, but not the hippocampus. Conversely, presynaptic inhibition by KORs of inhibitory synapses on D2 MSNs enhances integration of excitatory drive by the amygdala and hippocampus. In conclusion, we describe a circuit-based mechanism showing differential gating of afferent control of D1 and D2 MSN activity by KORs in a pathway-specific manner.
authors.affiliation: Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Tejeda
authors.affiliation: Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Wu
authors.affiliation: Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
authors.forename: Alana R
authors.initials: AR
authors.lastname: Kornspun
authors.affiliation: Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Pignatelli
authors.affiliation: Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
authors.forename: Vadim
authors.initials: V
authors.lastname: Kashtelyan
authors.affiliation: Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA; Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Krashes
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Brad B
authors.initials: BB
authors.lastname: Lowell
authors.affiliation: Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02578, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Carlezon
authors.affiliation: Synaptic Plasticity Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: antonello.bonci@nih.gov.
authors.forename: Antonello
authors.initials: A
authors.lastname: Bonci
mesh_terms: D000339:Affect / Q000502:physiology*; D000679:Amygdala / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D004399:Dynorphins / Q000378:metabolism* / Q000502:physiology; D005260:Female; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D009042:Motivation; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000502:physiology; D018408:Patch-Clamp Techniques; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D017473:Receptors, Opioid, kappa; D004399:Dynorphins
keywords: GABA; amygdala; dynorphin; electrophysiology; glutamate; hippocampus; hypothalamus