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The Journal of Neuroscience, November 1, 1998, 18(21):9139-9151
Dopamine Decreases the Excitability of Layer V Pyramidal Cells in
the Rat Prefrontal Cortex
Allan T.
Gulledge and
David B.
Jaffe
Division of Life Sciences, University of Texas at San Antonio, San
Antonio, Texas 78249
In both primates and rodents, the prefrontal cortex (PFC) is highly
innervated by dopaminergic fibers originating from the ventral
tegmental area, and activation of this mesocortical dopaminergic system
decreases spontaneous and evoked activity in the PFC in vivo. We have examined the effects of dopamine (DA), over a
range of concentrations, on the passive and active membrane properties of layer V pyramidal cells from the rat medial PFC (mPFC). Whole-cell and perforated-patch recordings were made from neurons in rat mPFC. As
a measure of cell excitability, trains of action potentials were evoked
with 1-sec-long depolarizing current steps. Bath application of
DA (0.05-30 µM) produced a reversible decrease in the
number of action potentials evoked by a given current step. In
addition, DA reversibly decreased the input resistance
(RN) of these cells. In a
subset of experiments, a transient increase in excitability was
observed after the washout of DA. Control experiments suggest that
these results are not attributable to changes in spontaneous synaptic activity, age-dependent processes, or strain-specific differences in dopaminergic innervation and physiology. Pharmacological analyses, using D1 agonists (SKF 38393 and SKF 81297), a D1 antagonist (SCH 23390), a D2 receptor agonist (quinpirole), and a D2 antagonist (sulpiride) suggest that decreases in spiking and
RN are mediated by D2 receptor activation.
Together, these results demonstrate that DA, over a range of
concentrations, has an inhibitory effect on layer V pyramidal neurons
in the rat mPFC, possibly through D2 receptor activation.
Key words:
dopamine; prefrontal cortex; electrophysiology; pyramidal
cell; whole-cell recording; perforated-patch recording
Copyright © 1998 Society for Neuroscience 0270-6474/98/18219139-13$05.00/0
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