NMDA receptor hypofunction, parvalbumin-positive neurons, and cortical gamma oscillations in schizophrenia

Schizophr Bull. 2012 Sep;38(5):950-7. doi: 10.1093/schbul/sbs010. Epub 2012 Feb 21.


Gamma oscillations appear to be dependent on inhibitory neurotransmission from parvalbumin (PV)-containing gamma-amino butyric acid neurons. Thus, the abnormalities in PV neurons found in schizophrenia may underlie the deficits of gamma-band synchrony in the illness. Because gamma-band synchrony is thought to be crucial for cognition, cognitive deficits in schizophrenia may reflect PV neuron dysfunction in cortical neural circuits. Interestingly, it has been suggested that PV alterations in schizophrenia are the consequence of a hypofunction of signaling through N-methyl-D-aspartate (NMDA) receptors (NMDARs). Here, we review recent findings that address the question of how NMDAR hypofunction might produce deficits of PV neuron-mediated inhibition in schizophrenia. We conclude that while dysregulation of NMDARs may play an important role in the pathophysiology of schizophrenia, additional research is required to determine the particular cell type(s) that mediate dysfunctional NMDAR signaling in the illness.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Awareness / physiology*
  • Cerebral Cortex / physiopathology*
  • Cholecystokinin / physiology
  • Cognition Disorders / physiopathology
  • Cortical Synchronization / physiology
  • Electroencephalography*
  • Glutamic Acid / physiology
  • Humans
  • Interneurons / physiology
  • Nerve Net / physiopathology
  • Neural Inhibition / physiology*
  • Neuronal Plasticity / physiology
  • Neurons / physiology*
  • Parvalbumins / physiology*
  • Pyramidal Cells / physiology
  • Receptors, AMPA / physiology
  • Receptors, GABA / physiology*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Schizophrenia / physiopathology*
  • Signal Transduction / physiology
  • Synaptic Transmission / physiology


  • Parvalbumins
  • Receptors, AMPA
  • Receptors, GABA
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Cholecystokinin