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1 Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
2 Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
3 Physiology and Neuroscience, University of South Carolina, Charleston, South Caroline, USA
4 Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
* To whom correspondence should be addressed. E-mail: gburgos{at}pitt.edu.
Dopaminergic regulation of primate dorsolateral prefrontal cortex (PFC) activity is essential for cognitive functions such as working memory. However, the cellular mechanisms of dopamine neuromodulation in PFC are not well understood. We have studied the effects of dopamine receptor activation during persistent stimulation of excitatory inputs onto fast-spiking GABAergic interneurons in monkey PFC. Stimulation at 20 Hz induced short-term EPSP depression. The D1 receptor agonist SKF81297 (5 µM) significantly reduced the amplitude of the first EPSP, but not of subsequent responses in EPSP trains, which still displayed significant depression. DA (10 µM) effects were similar to those of SKF81297, and were abolished by the D1 antagonist SCH23390 (5 µM), indicating a D1 receptor-mediated effect. DA did not alter miniature EPSCs, suggesting that its effects were activity- and presynaptic action potential-dependent. In contrast to previous findings in pyramidal neurons, in fast-spiking cells contribution of NMDA receptors to EPSPs at subthreshold potentials was not significant, and fast-spiking cell depolarization decreased EPSP duration. In addition, DA had no significant effects on temporal summation. The selective decrease in the amplitude of the first EPSP in trains delivered every 10 seconds, suggests that in FS neurons DA reduces the amplitude of EPSPs evoked at low frequency, but not of EPSPs evoked by repetitive stimulation. DA may therefore improve detection of EPSP bursts above background synaptic activity. EPSP bursts displaying short-term depression may transmit spike-timing dependent temporal codes contained in presynaptic spike trains. Thus, DA neuromodulation may increase the signal-to-noise ratio at fast-spiking cell inputs.
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