title: Dopamine D1-like receptor modulates layer- and frequency-specific short-term synaptic plasticity in rat prefrontal cortical neurons.
abstract: The mesocortical dopamine (DA) input to the prefrontal cortex (PFC) is crucial for processing short-term working memory (STWM) to guide forthcoming behavior. Short-term plasticity-like post-tetanic potentiation (PTP, < 3 min) and short-term potentiation (STP, < 10 min) may underlie STWM. Using whole-cell voltage-clamp recordings, mixed glutamatergic excitatory postsynaptic currents (EPSCs) evoked by layer III or layer V stimulation (0.5 or 0.067 Hz) were recorded from layer V pyramidal neurons. With 0.5 Hz basal stimulation of layer III, brief tetani (2 x 50 Hz) induced a homosynaptic PTP (decayed: approximately 1 min). The D1-like antagonist SCH23390 (1 microm) increased the PTP amplitude and decay time without inducing changes to the tetanic response. The tetani may evoke endogenous DA release, which activates a presynaptic D1-like receptor to inhibit glutamate release to modulate PTP. With a slower (0.067 Hz) basal stimulation, the same tetani induced STP (lasting approximately 4 min, but only at 2x intensity only) that was insignificantly suppressed by SCH23390. With stimulation of layer-V-->V inputs at 0.5 Hz, layer V tetani yielded inconsisitent responses. However, at 0.067 Hz, tetani at double the intensity resulted in an STP (lasting approximately 6 min), but a long-term depression after SCH23390 application. Endogenous DA released by tetanic stimulation can interact with a D1-like receptor to induce STP in layer V-->V synapses that receive slower (0.067 Hz) frequency inputs, but suppresses PTP at layer III-->V synapses that receive higher (0.5 Hz) frequency inputs. This D1-like modulation of layer- and frequency-specific synaptic responses in the PFC may contribute to STWM processing.
authors: Drug Discovery, Xenon Pharmaceuticals Inc., 3650 Gilmore Way, Burnaby, BC, Canada V5G 4W8.
authors: Clint E
authors: CE
authors: Young
authors: Charles R
authors: CR
authors: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019540:Area Under Curve; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017397:Prefrontal Cortex / Q000166:cytology*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D013826:Theta Rhythm / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1