Abnormal Gamma Oscillations in N-Methyl-D-Aspartate Receptor Hypofunction Models of Schizophrenia

Biol Psychiatry. 2016 May 1;79(9):716-726. doi: 10.1016/j.biopsych.2015.07.005. Epub 2015 Jul 17.

Abstract

N-methyl-D-aspartate receptor (NMDAR) hypofunction in parvalbumin-expressing (PV+) inhibitory neurons (INs) may contribute to symptoms in patients with schizophrenia (SZ). This hypothesis was inspired by studies in humans involving NMDAR antagonists that trigger SZ symptoms. Animal models of SZ using neuropharmacology and genetic knockouts have successfully replicated some of the key observations in human subjects involving alteration of gamma band oscillations (GBO) observed in electroencephalography and magnetoencephalography signals. However, it remains to be seen if NMDAR hypofunction in PV+ neurons is fundamental to the phenotype observed in these models. In this review, we discuss some of the key computational models of GBO and their predictions in the context of NMDAR hypofunction in INs. While PV+ INs have been the main focus of SZ studies in animal models, we also discuss the implications of NMDAR hypofunction in other types of INs using computational models for GBO modulation in the visual cortex.

Keywords: Computational models; Gamma oscillations; Inhibition; NMDA hypofunction; Parvalbumin; Schizophrenia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Action Potentials
  • Animals
  • Cerebral Cortex / physiopathology*
  • Electroencephalography
  • GABAergic Neurons / metabolism
  • GABAergic Neurons / physiology
  • Gamma Rhythm*
  • Humans
  • Interneurons / metabolism
  • Interneurons / physiology*
  • Models, Neurological*
  • Parvalbumins / metabolism
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Schizophrenia / physiopathology*
  • gamma-Aminobutyric Acid / physiology

Substances

  • Parvalbumins
  • Receptors, N-Methyl-D-Aspartate
  • gamma-Aminobutyric Acid