Dopamine D1 and D2 Receptors Make Dissociable Contributions to Dorsolateral Prefrontal Cortical Regulation of Rule-Guided Oculomotor Behavior

Authors

Susheel Vijayraghavan, 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.
Alex James Major, Graduate Program in Neuroscience, The University of Western Ontario, Robarts Research Institute, RRI 3203, 1151 Richmond Street North, London, ON N6A 5B7, Canada.
Stefan Everling, 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.

Document Type

Article

Publication Date

7-19-2016

Journal

Cell reports

Volume

16

Issue

3

First Page

805

Last Page

16

URL with Digital Object Identifier

10.1016/j.celrep.2016.06.031

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.