NMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex

Min Wang, Yang Yang, Ching Jung Wang, Nao J. Gamo, Lu E. Jin, James A. Mazer, John H. Morrison, Xiao Jing Wang, Amy F.T. Arnsten

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)736-749
Number of pages14
JournalNeuron
Volume77
Issue number4
DOIs
StatePublished - Feb 20 2013

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'NMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex'. Together they form a unique fingerprint.

  • Cite this

    Wang, M., Yang, Y., Wang, C. J., Gamo, N. J., Jin, L. E., Mazer, J. A., Morrison, J. H., Wang, X. J., & Arnsten, A. F. T. (2013). NMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex. Neuron, 77(4), 736-749. https://doi.org/10.1016/j.neuron.2012.12.032