Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons

^*Howard Hughes Medical Institute and Molecular and Computational Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037; ^‡Division of Basic Medical Sciences, University of South Dakota School of Medicine, 414 East Clark Street, Vermillion, SD 57069; and ^§Department of Biology, University of California at San Diego, La Jolla, CA 92093

Contributed by Charles F. Stevens

Abstract

Dopamine acts mainly through the D1/D5 receptor in the prefrontal cortex (PFC) to modulate neural activity and behaviors associated with working memory. To understand the mechanism of this effect, we examined the modulation of excitatory synaptic inputs onto layer V PFC pyramidal neurons by D1/D5 receptor stimulation. D1/D5 agonists increased the size of N-methyl-d-aspartate (NMDA) component of excitatory postsynaptic currents (EPSCs) through a postsynaptic mechanism. In contrast, D1/D5 agonists caused a slight reduction in the size of the non-NMDA component of EPSCs through a small decrease in release probability. With 20 Hz synaptic trains, we found that the D1/D5 agonists increased depolarization of summating the NMDA component of excitatory postsynaptic potential (EPSP). By increasing the NMDA component of EPSCs, yet slightly reducing release, D1/D5 receptor activation selectively enhanced sustained synaptic inputs and equalized the sizes of EPSPs in a 20-Hz train.

Footnotes

↵ † To whom reprint requests should be addressed. E-mail: jeremy{at}salk.edu.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.011518798.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.011518798
Abbreviations:

PFC,

prefrontal cortex;

NMDA,

N-methyl-d-aspartate;

ACSF,

artificial cerebrospinal fluid;

EPSC,

excitatory postsynaptic current;

mEPSC,

mini-EPSC;

EPSP,

excitatory postsynaptic potential;

APV,

2-amino-5-phosphonovaleric acid