title: Cholinergic modulation of working memory activity in primate prefrontal cortex.
abstract: The prefrontal cortex, a cortical area essential for working memory and higher cognitive functions, is modulated by a number of neurotransmitter systems, including acetylcholine; however, the impact of cholinergic transmission on prefrontal activity is not well understood. We relied on systemic administration of a muscarinic receptor antagonist, scopolamine, to investigate the role of acetylcholine on primate prefrontal neuronal activity during execution of working memory tasks and recorded neuronal activity with chronic electrode arrays and single electrodes. Our results indicated a dose-dependent decrease in behavioral performance after scopolamine administration in all the working memory tasks we tested. The effect could not be accounted for by deficits in visual processing, eye movement responses, or attention, because the animals performed a visually guided saccade task virtually error free, and errors to distracting stimuli were not increased. Performance degradation under scopolamine was accompanied by decreased firing rate of the same cortical sites during the delay period of the task and decreased selectivity for the spatial location of the stimuli. These results demonstrate that muscarinic blockade impairs performance in working memory tasks and prefrontal activity mediating working memory.
authors.affiliation: Dept. of Neurobiology and Anatomy, Wake Forest Univ. School of Medicine, Medical Center Blvd., Winston Salem, NC 27157, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Xue-Lian
authors.initials: XL
authors.lastname: Qi
authors.forename: Kristy
authors.initials: K
authors.lastname: Douglas
authors.forename: Kathini
authors.initials: K
authors.lastname: Palaninathan
authors.forename: Hyun Sug
authors.initials: HS
authors.lastname: Kang
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Buccafusco
authors.forename: David T
authors.initials: DT
authors.lastname: Blake
authors.forename: Christos
authors.initials: C
authors.lastname: Constantinidis
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D059329:Cholinergic Neurons / Q000187:drug effects / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology; D004567:Electrodes, Implanted; D004594:Electrophysiology / Q000379:methods; D008253:Macaca mulatta; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012438:Saccades / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology; D013028:Space Perception / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018727:Muscarinic Antagonists; D012601:Scopolamine; D000109:Acetylcholine