FIG. 6.

Summary of the changes induced to neural circuits as a consequence of NMDAR blockade. PV+ and pyramidal neuronal populations are represented by the dark-colored circles and light-colored triangles, respectively. In normally developed circuits, balanced excitatory and inhibitory connections between and within the two types of neurons give rise to gamma-oscillations required for cognitive functions. Acute blockade of NMDARs, without causing structural alterations to the circuit, preferentially suppresses the activity of PV+ neurons, leading to disinhibition of pyramidal neurons, which produces elevated gamma-activities and models psychotic episodes of schizophrenia. Chronic and developmental blockade of NMDARs, on the other hand, activate the IL-6/Nox2 pathway illustrated in Figure 5, rendering the PV+ neurons hypofunctional, and eventually leading to abnormal weights of synaptic connections in the network. This, in turn, generates a phenotype that recapitulates some negative and cognitive symptoms of schizophrenia, such as deficient gamma activities.