Stimulation of D1-type dopamine receptors enhances excitability in prefrontal cortical pyramidal neurons in a state-dependent manner

Prefrontal cortex neurons recorded in vivo exhibit bistable activity states ! consisting of a depolarized phase (-55 mV) and a hyperpolarized phase (-8 5 mV). These "up" and "down" states have durations ranging from 800 ms to 1 s and a periodicity of approximately 1 Hz. This study examines the state-d ependency of prefrontal cortical neuron responses to dopamine, in which the bistable-state was approximated in vitro by intracellular current injectio n. At resting membrane potential (n = 10), dopamine caused a significant de polarization of the membrane potential without altering any of the other el ectrophysiological characteristics tested. In contrast, both dopamine (30 m uM, 5 min) and the D1 receptor agonist SKF 38393 (5 and 10 muM) increased c ell excitability when the cell was in the depolarized state (i.e., -55 mV) but not the hyperpolarized state (i.e., -85 mV: n = 10). This increase in e xcitability was accompanied by a decrease in the rheobase current. The SKF 38393-enhanced excitability was dose-dependent and could be blocked by bath administration of the D1 receptor antagonist SCH 23390 (5 and 10 muM) Admi nistration of the GABA antagonist bicuculline (7 muM) plus the N-methyl-D-a spartate channel blocker CPP (10 muM) produced an additional increase in th e excitability of prefrontal cortex neurons that was not dependent on the m embrane potential. From these data we suggest that dopamine exerts state-dependent modulatory effects on the excitability of neurons in deep layers of the prefrontal cor tex. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.