THE EFFECTS OF DOPAMINE ON THE SUBTHRESHOLD ELECTROPHYSIOLOGICAL RESPONSES OF RAT PREFRONTAL CORTEX NEURONS IN-VITRO

The rat prefrontal cortex is densely innervated by dopaminergic fibres originating in the mesencephalic ventral tegmental area, and dopamine application in vivo has an inhibitory effect. We have studied the eff ects of dopamine on the persistent sodium current that is present in p refrontal cortex neurons and on the subthreshold electrophysiological responses generated by that current: a slow depolarization and a fast oscillatory activity. Experiments were made in coronal slices of rat f rontal cortex (300-400 mu m thickness) and intracellular recordings fr om regularly spiking cells were obtained with 3 M potassium acetate-fi lled glass microelectrodes (80-150 M Omega). Dopamine was applied diss olved in the extracellular medium and, in current-clamp recordings, re versibly inhibited the slow subthreshold depolarization. Dopamine was ineffective when applied after tetrodotoxin (1 mu M) had blocked the a ction potentials. This inhibition was dose-dependent in the range of 0 .1-10 mu M. Dopamine, applied at 10 mu M, decreased the steady-state f iring frequency and also inhibited the subthreshold fast oscillatory a ctivity. The currents activated in the subthreshold range were recorde d with the single-electrode voltage-clamp technique and a clear persis tent, tetrodotoxin-sensitive component was isolated. This component wa s inhibited by 50% in a reversible way by 20 mu M dopamine. These resu lts show that dopamine increases the threshold for spike firing and su ggest a mechanism for the inhibitory action of this neurotransmitter i n the prefrontal cortex.