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 language | English (US) |
|---|---|
| Pages (from-to) | 736-749 |
| Number of pages | 14 |
| Journal | Neuron |
| Volume | 77 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 20 2013 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
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NMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex. / Wang, Min; Yang, Yang; Wang, Ching Jung; Gamo, Nao J.; Jin, Lu E.; Mazer, James A.; Morrison, John H.; Wang, Xiao Jing; Arnsten, Amy F.T.
In: Neuron, Vol. 77, No. 4, 20.02.2013, p. 736-749.Research output: Contribution to journal › Article
TY - JOUR
T1 - NMDA Receptors Subserve Persistent Neuronal Firing during Working Memory in Dorsolateral Prefrontal Cortex
AU - Wang, Min
AU - Yang, Yang
AU - Wang, Ching Jung
AU - Gamo, Nao J.
AU - Jin, Lu E.
AU - Mazer, James A.
AU - Morrison, John H.
AU - Wang, Xiao Jing
AU - Arnsten, Amy F.T.
PY - 2013/2/20
Y1 - 2013/2/20
N2 - 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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=84874286656&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874286656&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2012.12.032
DO - 10.1016/j.neuron.2012.12.032
M3 - Article
C2 - 23439125
AN - SCOPUS:84874286656
VL - 77
SP - 736
EP - 749
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -