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PMID: 23439125 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex.

Neuron ·Vol. 77 ·No. 4 ·2013-02-20 ·Pages 736-49

Wang M, Yang Y, Wang CJ, Gamo NJ, Jin LE, Mazer JA, Morrison JH, Wang XJ, Arnsten AF

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.

MeSH Terms
Animals Brain Mapping Computer Simulation Macaca mulatta Male Memory, Short-Term/physiology Models, Neurological Neurons/physiology Prefrontal Cortex/physiology Pyramidal Cells/physiology Receptors, AMPA/physiology Receptors, N-Methyl-D-Aspartate/physiology
Chemicals
NR2B NMDA receptor Receptors, AMPA Receptors, N-Methyl-D-Aspartate
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Wang Min
Department Neurobiology, Yale Medical School, New Haven, CT 06510, USA.
Yang Yang
Wang Ching-Jung
Gamo Nao J
Jin Lu E
Mazer James A
Morrison John H
Wang Xiao-Jing
Arnsten Amy F T
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2012.12.032
Published
2013-02-20
Pages
736-49
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC3584418
Subset
IM
Grants
NIA NIH HHS · P01 AG030004 · United States
NIMH NIH HHS · R01 MH062349 · United States
NIA NIH HHS · R37 AG006647 · United States
NIMH NIH HHS · MH 09335401 · United States
NCRR NIH HHS · U54RR024350 · United States
NIA NIH HHS · P01 AG016765 · United States
NIA NIH HHS · AG016765 · United States
NIMH NIH HHS · MH062349 · United States
NIMH NIH HHS · R01 MH093354 · United States
NIA NIH HHS · AG06647 · United States
NIAAA NIH HHS · RL1AA017536 · United States
NIAAA NIH HHS · RL1 AA017536 · United States
Corrections
CommentIn
PMID: 23439115
External Links
PubMed source DOI: 10.1016/j.neuron.2012.12.032 PMC Full Text View journal details
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