title: Dopamine D1 and D2 Receptors Make Dissociable Contributions to Dorsolateral Prefrontal Cortical Regulation of Rule-Guided Oculomotor Behavior.
abstract: Studies of neuromodulation of spatial short-term memory have shown that dopamine D1 receptor (D1R) stimulation in dorsolateral prefrontal cortex (DLPFC) dose-dependently modulates memory activity, whereas D2 receptors (D2Rs) selectively modulate activity related to eye movements hypothesized to encode movement feedback. We examined localized stimulation of D1Rs and D2Rs on DLPFC neurons engaged in a task involving rule representation in memory to guide appropriate eye movements toward or away from a visual stimulus. We found dissociable effects of D1R and D2R on DLPFC physiology. D1R stimulation degrades memory activity for the task rule and increases stimulus-related selectivity. In contrast, D2R stimulation affects motor activity tuning only when eye movements are made to the stimulus. Only D1R stimulation degrades task performance and increases impulsive responding. Our results suggest that D1Rs regulate rule representation and impulse control, whereas D2Rs selectively modulate eye-movement-related dynamics and not rule representation in the DLPFC.
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, Medical Sciences Building, Room 216, London, ON N6A 5C1, Canada.
authors.forename: Susheel
authors.initials: S
authors.lastname: Vijayraghavan
authors.affiliation: Graduate Program in Neuroscience, The University of Western Ontario, Robarts Research Institute, RRI 3203, 1151 Richmond Street North, London, ON N6A 5B7, Canada.
authors.forename: Alex James
authors.initials: AJ
authors.lastname: Major
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, Medical Sciences Building, Room 216, London, ON N6A 5C1, Canada; Graduate Program in Neuroscience, The University of Western Ontario, Robarts Research Institute, RRI 3203, 1151 Richmond Street North, London, ON N6A 5B7, Canada; Robarts Research Institute, The University of Western Ontario, Room EB-120, 1151 Richmond Street North, London, ON N6A 5B7, Canada. Electronic address: severlin@uwo.ca.
authors.forename: Stefan
authors.initials: S
authors.lastname: Everling
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D005133:Eye Movements / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine