Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

摘要: Many risk genes interact synergistically to produce schizophrenia and many neurotransmitter interactions have been implicated. We developed a circuit-based framework for understanding gene interactions. NMDAR hypofunction has implicated in because antagonists reproduce symptoms of the disease. One action is reduce excitation fast-spiking interneurons, resulting disinhibition pyramidal cells. Overactive cells, notably those hippocampus, can drive hyperdopaminergic state that produces psychosis. Additional aspects interneuron function be understood this framework, as follows. (i) In animal models, parvalbumin GAD67, found schizophrenia. These changes further viewed aberrant response homeostatic system having faulty activity sensor (the NMDAR). (ii) Disinhibition decreases power gamma oscillation might thereby negative cognitive symptoms. (iii) Nicotine enhances output contribute its therapeutic effect