Mathematical Modeling of Schizophrenia

Abnormal brain function in schizophrenia involves an extended network of brain structures. In schizophrenia, an abnormal dopamine activity in accordance with altered GABA and glutamate transmission appears to interfere with this process. In this study, we have examined the effect of dopamine hyperactivity on CA3 pyramidal cells using a mathematical model. Our simulation results show that while normal activity of dopamine system causes the membrane potential of pyramidal cell to display a periodic bursting behavior, hyperactivity of this system brings about irregular and aperiodic patterns of activity. In addition, it is suggested that hypo-glutamatergic conditions result in reduced activation of the striatal complex and may induce psychotic symptoms. Thus, we also investigated the role of glutamate level in postsynaptic cell activity. Simulation results indicate that hypo-glutamatergic condition has the same effect on the membrane potential of pyramidal cells, i.e. aperiodic and irregular firing patterns. Based on these results, we hypothesize that glutamate receptor activation may have good therapeutic results in schizophrenia.