Presynaptic D1Dopamine Receptors in Primate Prefrontal Cortex: Target-Specific Expression in the Glutamatergic Synapse

Abstract

Dopaminergic modulation of glutamate neurotransmission in prefrontal cortex (PFC) microcircuits is commonly perceived as a basis for cognitive operations. Yet it appears that although the control of recurrent excitation between deep-layer prefrontal pyramids may involve presynaptic and postsynaptic D 1 receptor (D 1 R) mechanisms, pyramid-to-interneuron communication will engage a postsynaptic D 1 R component. The substrate underlying such target-specific neuromodulatory patterns was investigated in the infragranular PFC with immunoelectron microscopy for D 1 R and parvalbumin, a marker for fast-spiking interneurons. In addition to their proverbial postsynaptic expression, gold-labeled D 1 Rs were distinctly distributed on perisynaptic/extrasynaptic membranes and the axoplasm of 13% of excitatory-like, presumably glutamatergic varicosities. Most importantly, presynaptic D 1 Rs were highly specific with regard to the cellular compartment and neurochemical identity of the postsynaptic neuron, being present in spine-targeting varicosities but distinctly absent from those synapsing with parvalbumin profiles often coexpressing D 1 Rs. We define therein an axonal D 1 heteroreceptor component, apparently mediating volume neurotransmission, yet strategically positioned to convey target cell-specific modulation of the glutamatergic drive. We also indicate that presynaptic D 1 R mechanisms may indeed be associated with recurrent excitation in prefrontal microcircuits, consistent with physiological evidence for a role of these receptors in modulating the persistent activity-profile of neurons essential for working memory.