Section of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510
Contributed by Patricia S. Goldman-Rakic, November 1, 2000
The prefrontal cortex plays a fundamental role in the working
memory functions of the cerebral cortex and is also the site of
dysfunction in several neurological and psychiatric disorders, including schizophrenia. Prefrontal neurons are distinguished by their
capacity for sustained activity during the time a stimulus is held in
memory, and this mnemonic response is considered a substrate for a
variety of cognitive functions. The neuronal basis for sustained
activity in prefrontal neurons is unknown but is thought to involve
recurrent excitation among pyramidal neurons. Recent studies in awake
behaving monkeys have demonstrated that the persistent activity in
prefrontal neurons is modulated by dopamine. To examine the mechanisms
by which dopamine might modulate transmission in local excitatory
circuits, we have performed dual whole-cell recordings in connected
pyramidal cell pairs with and without dopamine application. We find
that dopamine reduces the efficacy of unitary excitatory
neurotransmission in layer V pyramidal cells by decreasing its
reliability. These effects, which are reproduced by a selective D1
agonist and blocked by a D1 antagonist, are independent of voltage
changes and are not attenuated by blockade of sodium and potassium
channels in the postsynaptic neurons. We conclude that attenuation of
local horizontal excitatory synaptic transmission in layer V pyramidal
neurons by dopamine is through D1 actions at a presynaptic site.
Neurobiology
Presynaptic regulation of recurrent excitation by D1 receptors in
prefrontal circuits
*
To whom reprint requests should be addressed. E-mail:
patricia.goldman-rakic{at}yale.edu.
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