Influence of NMDA and GABA synaptic dysfunction on the evoked gamma oscillations in a computational model of Schizophrenia

Schizophrenia is a psychiatric disorder which is characterized by delusions, hallucinations, and affects thoughts, behavior and emotions. Major neuronal degeneration is not observed in schizophrenic patients, but abnormalities in cortical circuits are present. These abnormalities are reflected in impaired EEG gamma frequency (30-80Hz), being crucial for many processes including sensation, perception, working memory and attention. NMDA and GABA synaptic dysfunction are proposed as one of the possible mechanisms underlying the decreased gamma frequency oscillations in schizophrenia. We use a computational modeling approach to investigate the influence of NMDA and GABA synaptic dysfunction on the evoked gamma oscillations in cortex. We employ a model of a spiking neural network composed of 800 pyramidal neurons (PCs), 150 regular-spiking interneurons (RSIs) and 50 fast-spiking interneurons (FSIs) [1]. All cells are randomly interconnected. The background activity in the cortex is represented by an independent Poisson noise input to network neurons at 4 Hz. Sensory drive stimulus is modeled as excitatory stimulation of the network neurons at 40Hz. GABA receptor-gated channel time constant of FSIs is increased, and NMDA receptor-gated channel weight of FSIs is decreased to represent synaptic dysfunction in schizophrenia. Prolonged decay time of GABA receptor-gated channels and decreased weight of NMDA receptor-gated channels onto FSIs lead to the impaired network activity: oscillation power is decreased at 40Hz and increased at 20Hz in PCs. The effect of synaptic GABA impairment is more profound NMDA and GABA synaptic dysfunction leads to the decreased gamma frequency oscillations in a spiking neural network of cortex. Computational modeling approach is a powerful tool to understand complex non-linear dynamical systems and intrinsic mechanisms of neuronal network activity in healthy and diseased brainGamtos mokslų fakultetasLietuvos sveikatos mokslų universitetasTaikomosios informatikos katedraVytauto Didžiojo universiteta