Molecular analysis of glutamatergic neurotransmission in hepatic encephalopathy (B05)

• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2012 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190586431

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.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 974: Communication and System Relevance in Liver Injury and Regeneration
• Applicant Institution: Heinrich-Heine-Universität Düsseldorf
• Project Head: Professor Dr. Nikolaj Klöcker