BehavioralSystemsCognitive….pdfVIP

The Journal of Neuroscience, May 18, 2005 • 25(20):5013–5023 • 5013 Behavioral/Systems/Cognitive Mesocortical Dopamine Neurons Operate in Distinct Temporal Domains Using Multimodal Signaling 1 1 1 2 3 Antonieta Lavin, * Lourdes Nogueira, * Christopher C. Lapish, * R. Mark Wightman, Paul E. M. Phillips, and Jeremy K. Seamans1 1 2 Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599, and 3Department of Psychiatry and Behavioral Sciences and Department of Pharmacology, University of Washington, Seattle, Washington 98195 In vivo extracellular recording studies have traditionally shown that dopamine (DA) transiently inhibits prefrontal cortex (PFC) neurons, yet recent biophysical measurements in vitro indicate that DA enhances the evoked excitability of PFC neurons for prolonged periods. Moreover, although DA neurons apparently encode stimulus salience by transient alterations in firing, the temporal properties of the PFC DA signal associated with various behaviors is often extraordinarily prolonged. The present study used in vivo electrophysiological and electrochemical measures to show that the mesocortical system produces a fast non-DA-mediated postsynaptic response in the PFC that appears to be initiated by glutamate. In contrast, short burst stimulation of mesocortical DA neurons that produced transient (4 s) DA release in the PFC caused a simultaneous reduction in spontaneous firing (consistent with extracellular in vivo recor