Gamma oscillation deficits and the onset and early progression of schizophrenia

Abstract

A fascinating convergence of evidence in recent years has implicated the disturbances of neural synchrony in the gamma frequency band (30-100 Hz) as a major pathophysiologic feature of schizophrenia. Evidence suggests that reduced glutamatergic neurotransmission via the N-methyl-D-aspartate (NMDA) receptors that are localized to inhibitory interneurons, perhaps especially the fast-spiking cells that contain the calcium-binding protein parvalbumin (PV), may contribute to gamma band synchrony deficits. These deficits may underlie the brain's failure to integrate information and hence the manifestations of many symptoms and deficits of schizophrenia. Furthermore, because gamma oscillations are thought to provide the temporal structure that is necessary for synaptic plasticity, gamma oscillation deficits may disturb the developmental synaptic reorganization process that is occurring during the period of late adolescence and early adulthood. This disturbance may contribute to the onset of schizophrenia and the functional deterioration that is characteristic of the early stage of the illness. Finally, reduced NMDA neurotransmission on inhibitory interneurons, including the PV-containing cells, may inflict excitotoxic or oxidative injury to downstream pyramidal neurons, leading to further loss of synapses and dendritic branchings. Hence, a key element in the conceptualization of rational early-intervention and prevention strategies for schizophrenia may involve correcting the abnormal NMDA neurotransmission on inhibitory interneurons-possibly that on the PV-containing neurons, in particular-thereby normalizing gamma oscillation deficits and attenuating downstream neuronal pathology.