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Brief Communications

NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons

Houman Homayoun and Bita Moghaddam
Journal of Neuroscience 24 October 2007, 27 (43) 11496-11500; DOI: https://doi.org/10.1523/JNEUROSCI.2213-07.2007
Houman Homayoun
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Bita Moghaddam
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Abstract

NMDA receptors mediate excitatory postsynaptic potentials throughout the brain but, paradoxically, NMDA receptor antagonists produce cortical excitation in humans and behaving rodents. To elucidate a mechanism for these diverging effects, we examined the effect of use-dependent inhibition of NMDA receptors on the spontaneous activity of putative GABA interneurons and pyramidal neurons in the prefrontal cortex of awake rats. We find that inhibition of NMDA receptors predominately decreases the activity of putative GABA interneurons but, at a delayed rate, increases the firing rate of the majority of pyramidal neurons. Thus, NMDA receptors preferentially drive the activity of cortical inhibitory interneurons suggesting that NMDA receptor inhibition causes cortical excitation by disinhibition of pyramidal neurons. These findings support the hypothesis that NMDA receptor hypofunction, which has been implicated in the pathophysiology of schizophrenia, diminishes the inhibitory control of PFC output neurons. Reducing this effect may be critical for treatment of schizophrenia.

  • schizophrenia
  • glutamate
  • GABA
  • ensemble unit recording
  • antipsychotic drugs
  • metabotropic glutamate receptors
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The Journal of Neuroscience: 27 (43)
Journal of Neuroscience
Vol. 27, Issue 43
24 Oct 2007
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NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons
Houman Homayoun, Bita Moghaddam
Journal of Neuroscience 24 October 2007, 27 (43) 11496-11500; DOI: 10.1523/JNEUROSCI.2213-07.2007

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NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons
Houman Homayoun, Bita Moghaddam
Journal of Neuroscience 24 October 2007, 27 (43) 11496-11500; DOI: 10.1523/JNEUROSCI.2213-07.2007
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