Effects of NMDA Receptor Hypofunction on Inhibitory Control in a Two-Layer Neural Circuit Model

Abstract

Inhibitory control plays an important role in controlling behaviors, and its impairment is a characteristic feature of schizophrenia. Such inhibitory control has been examined through the the stop-signal task, wherein participants are asked to suppress a planned movement when a stop signal appears. In this research, we constructed a two-layer spiking neural circuit model to study how N-methyl-D-aspartate receptor (NMDAR) hypofunction, a potential pathological mechanism in schizophrenia, impacts the inhibitory control ability in the stop-signal task. To find the possible NMDAR hypofunction effects in schizophrenia, all NMDA-mediated synapses in the model were set to be NMDAR hypofunction at different levels. Our findings revealed that the performances of the stop-signal task were close to the experimental results in schizophrenia when NMDAR hypofunction was present in the neurons of two populations that controlled the “go” process and the “stop” process of the stop-signal task, implying that the execution and inhibition of behaviors were both impaired in schizophrenia. Under a certain degree of NMDAR hypofunction, the circuit model is able to replicate the stop-signal task performances observed in individuals with schizophrenia. In addition, we have observed a predictable outcome indicating that NMDAR hypofunction can lower the saccadic threshold in the stop-signal task. These results provide a mechanical explanation for the impairment of inhibitory control in schizophrenia.