title: Presynaptic regulation of recurrent excitation by D1 receptors in prefrontal circuits.
abstract: 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.
authors.affiliation: Section of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Gao
authors.forename: L S
authors.initials: LS
authors.lastname: Krimer
authors.forename: P S
authors.initials: PS
authors.lastname: Goldman-Rakic
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005289:Ferrets / Q000502:physiology; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D020891:Raclopride / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012559:Schizophrenia / Q000503:physiopathology; D015222:Sodium Channels / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D014851:Wakefulness / Q000502:physiology
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D015221:Potassium Channels; D017447:Receptors, Dopamine D1; D015222:Sodium Channels; D020891:Raclopride; D004298:Dopamine