title: NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex.
abstract: Neurons in the primate dorsolateral prefrontal cortex (dlPFC) generate persistent firing in the absence of sensory stimulation, the foundation of mental representation. Persistent firing arises from recurrent excitation within a network of pyramidal Delay cells. Here, we examined glutamate receptor influences underlying persistent firing in primate dlPFC during a spatial working memory task. Computational models predicted dependence on NMDA receptor (NMDAR) NR2B stimulation, and Delay cell persistent firing was abolished by local NR2B NMDAR blockade or by systemic ketamine administration. AMPA receptors (AMPARs) contributed background depolarization to sustain network firing. In contrast, many Response cells were sensitive to AMPAR blockade and increased firing after systemic ketamine, indicating that models of ketamine actions should be refined to reflect neuronal heterogeneity. The reliance of Delay cells on NMDAR may explain why insults to NMDARs in schizophrenia or Alzheimer's disease profoundly impair cognition.
authors: Department Neurobiology, Yale Medical School, New Haven, CT 06510, USA.
authors: Min
authors: M
authors: Wang
authors: Yang
authors: Y
authors: Yang
authors: Ching-Jung
authors: CJ
authors: Wang
authors: Nao J
authors: NJ
authors: Gamo
authors: Lu E
authors: LE
authors: Jin
authors: James A
authors: JA
authors: Mazer
authors: John H
authors: JH
authors: Morrison
authors: Xiao-Jing
authors: XJ
authors: Wang
authors: Amy F T
authors: AF
authors: Arnsten
mesh_terms: D000818:Animals; D001931:Brain Mapping; D003198:Computer Simulation; D008253:Macaca mulatta; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: C121001:NR2B NMDA receptor; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate