dopamine modulates persistent synaptic activity and enhances the signal-to-noise ratio in the prefrontal cortex多巴胺调节持久的突触活动和提高信噪比的前额叶皮层.pdfVIP

Dopamine Modulates Persistent Synaptic Activity and Enhances the Signal-to-Noise Ratio in the Prefrontal Cortex 1 1 2 3 Sven Kroener *, L. Judson Chandler , Paul E. M. Phillips , Jeremy K. Seamans 1 Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, United States of America, 2 Department of Psychiatry and Behavioral Science, University of Washington, Seattle, Washington, United States of America, 3 Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada Abstract Background: The importance of dopamine (DA) for prefrontal cortical (PFC) cognitive functions is widely recognized, but its mechanisms of action remain controversial. DA is thought to increase signal gain in active networks according to an inverted U dose-response curve, and these effects may depend on both tonic and phasic release of DA from midbrain ventral tegmental area (VTA) neurons. Methodology/Principal Findings: We used patch-clamp recordings in organotypic co-cultures of the PFC, hippocampus and VTA to study DA modulation of spontaneous network activity in the form of Up-states and signals in the form of synchronous EPSP trains. These cultures possessed a tonic DA level and stimulation of the VTA evoked DA transients within the PFC. The addition of high ($1 mM) concentrations of exogenous DA to the cultures reduced Up-states and diminished excitatory synaptic inputs (EPSPs) evoked during the Down-state. Increasing endogenous DA via bath application of cocaine also reduced Up-states. Lower concentrations of exogenous DA (0.1 mM) had no effect on the up-state itself,