title: Protein kinase C overactivity impairs prefrontal cortical regulation of working memory.
abstract: The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.
authors.affiliation: Department of Neurobiology, Yale Medical School, 333 Cedar Street, New Haven, CT 06520-8001, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Birnbaum
authors.forename: P X
authors.initials: PX
authors.lastname: Yuan
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Vijayraghavan
authors.forename: A K
authors.initials: AK
authors.lastname: Bloom
authors.forename: D J
authors.initials: DJ
authors.lastname: Davis
authors.forename: K T
authors.initials: KT
authors.lastname: Gobeske
authors.forename: J D
authors.initials: JD
authors.lastname: Sweatt
authors.forename: H K
authors.initials: HK
authors.lastname: Manji
authors.forename: A F T
authors.initials: AF
authors.lastname: Arnsten
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D002243:Carbolines / Q000494:pharmacology; D004594:Electrophysiology; D004789:Enzyme Activation; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D016651:Lithium Carbonate / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010617:Phenanthridines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000201:enzymology / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D015398:Signal Transduction; D013312:Stress, Physiological / Q000503:physiopathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000470:Alkaloids; D053119:Benzophenanthridines; D002243:Carbolines; D007093:Imidazoles; D010617:Phenanthridines; D018340:Receptors, Adrenergic, alpha-1; D016651:Lithium Carbonate; C035874:FG 7142; D014635:Valproic Acid; C016299:chelerythrine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C014282:cirazoline