title: Cue-Evoked Dopamine Release Rapidly Modulates D2 Neurons in the Nucleus Accumbens During Motivated Behavior.
abstract: Dopaminergic neurons that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) fire in response to unpredicted rewards or to cues that predict reward delivery. Although it is well established that reward-related events elicit dopamine release in the NAc, the role of rapid dopamine signaling in modulating NAc neurons that respond to these events remains unclear. Here, we examined dopamine's actions in the NAc in the rat brain during an intracranial self-stimulation task in which a cue predicted lever availability for electrical stimulation of the VTA. To distinguish actions of dopamine at select receptors on NAc neurons during the task, we used a multimodal sensor that probes three aspects of neuronal communication simultaneously: neurotransmitter release, cell firing, and identification of dopamine receptor type. Consistent with prior studies, we first show dopamine release events in the NAc both at cue presentation and after lever press (LP). Distinct populations of NAc neurons encode these behavioral events at these same locations selectively. Using our multimodal sensor, we found that dopamine-mediated responses after the cue involve exclusively a subset of D2-like receptors (D2Rs), whereas dopamine-mediated responses proximal to the LP are mediated by both D1-like receptors (D1R) and D2Rs. These results demonstrate for the first time that dopamine-mediated responses after cues that predict reward availability are specifically linked to its actions at a subset of neurons in the NAc containing D2Rs.
  
  
  
  Successful reward procurement typically involves the completion of a goal-directed behavior in response to appropriate environmental cues. Although numerous studies link the mesolimbic dopamine system with these processes, how dopamine's effects are mediated on the receptor level within a key neural substrate, the nucleus accumbens, remains elusive. Here, we used a unique multimodal sensor that reveals three aspects of neuronal interactions: neurotransmitter release, cell firing, and dopamine-receptor type. We identified a key role of D2-like receptor (D2R)-expressing neurons in response to a reward-predicting cue, whereas both the D2R and D1R types modulate responses of neurons proximal to the goal-directed action. This work provides novel insight into the unique role of D2R-mediated neuronal activity to reward-associated cues, a fundamental aspect of motivated behaviors.
authors.affiliation: Department of Chemistry.
authors.forename: Catarina
authors.initials: C
authors.lastname: Owesson-White
authors.affiliation: Department of Chemistry.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Belle
authors.affiliation: Department of Chemistry.
authors.forename: Natalie R
authors.initials: NR
authors.lastname: Herr
authors.affiliation: Department of Chemistry.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Peele
authors.affiliation: Department of Chemistry.
authors.forename: Preethi
authors.initials: P
authors.lastname: Gowrishankar
authors.affiliation: Department of Psychology and Neuroscience, and Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Carelli
authors.affiliation: Department of Chemistry, Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 rmw@unc.edu.
authors.forename: R Mark
authors.identifier: 0000-0003-2198-139X
authors.initials: RM
authors.lastname: Wightman
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D003463:Cues; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D006040:Goals; D007478:Iontophoresis; D008297:Male; D009042:Motivation / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012653:Self Stimulation; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D004298:Dopamine
keywords: dopamine; dopamine receptors; electrophysiology; iontophoresis; reward anticipation; voltammetry