Molecular analysis of glutamatergic neurotransmission in hepatic encephalopathy (B05)

在神经胶质共培养模型中，高氨降低AMPA受体（AMPARs）的神经元表达。然而，基础谷氨酸能神经传递完全维持在突触外ampar的代价下，后者不再可用于突触增强。本研究将检验肝性脑病（HE）动物模型中突触可塑性的限制是否由于ampar突触外储备池的减少而导致临床HE认知缺陷的假设。利用超分辨率显微镜和单粒子跟踪，我们将在高氨条件下可视化AMPAR，以建立突触后AMPAR在HE中的运输的定量模型，由此可以推断出治疗策略。

High ammonia reduces neuronal expression of AMPA receptors (AMPARs) in a neuroglial co-culture model. Yet, basal glutamatergic neurotransmission is fully maintained at the expense of extrasynaptic AMPARs, which are no longer available for synaptic potentiation. Here, the hypothesis will be tested, whether the constraints of synaptic plasticity in animal models of hepatic encephalopathy (HE), that might cause the cognitive deficits in clinical HE, are due to a reduction in the extrasynaptic reserve pool of AMPARs. Employing superresolution microscopy and single particle tracking, we will visualize AMPARs under conditions of high ammonia to develop a quantitative model of postsynaptic AMPAR trafficking in HE, from which treatment strategies might be deduced.