1. ¹Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA
2. ²Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA

Correspondence: Dr S-P Onn, Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA. Tel: +1 215 991 8408; Fax: +1 215 843 9082; E-mail: Shao-Pii.Onn@drexel.edu

Received 14 January 2005; Revised 26 May 2005; Accepted 3 June 2005; Published online 27 July 2005.

Abstract

Although dopamine (DA) effects in the prefrontal cortex (PFC) have been studied extensively, the function of steady-state ambient levels of DA in the regulation of afferent excitatory transmission in PFC pyramidal neurons remains relatively unexplored. Using intracellular sharp-electrode and whole-cell recordings combined with intracellular labeling in brain slices, we found that D1/D5 receptor blockade did not alter synaptic responses in the PFC, but D1/D5 receptor activation consistently enhanced recurrent synaptic excitation in the majority of pyramidal neurons tested. In contrast, D4 receptor blockade resulted in an evoked complex multiple spike discharge pattern that contained both early and late (presumably multisynaptic) components of the evoked response that is contingent upon the preservation of axon collaterals of the neuron under study. Moreover, GABAergic interneurons were found to play a role in both responses; blockade of GABA_a-mediated inhibition caused bath application of DA to convert monosynaptic excitatory postsynaptic potentials (EPSPs) to complex spike bursts riding on the late component of the EPSP. On the other hand, during the blockade of GABA_a-mediated conductances, administration of a D4 receptor antagonist failed to facilitate evoked multiple spike discharge. Morphological analysis of axon collaterals of labeled neurons revealed that neurons in which the D4 receptor blockade induced the putative polysynaptic response had axon collaterals that were largely preserved. These data suggest that DA exerts a bidirectional modulation of PFC pyramidal neurons in brain slices provided that local network connections with interneurons are preserved, with D4 receptors under tonic stimulation by ambient low levels of DA, whereas D1/D5 receptors activated upon phasic DA input.