Mathematical models of protein receptor trafficking in dendrites

University Of Utah, Salt Lake City UT

Investigators

Abstract

Neurons are amongst the largest and most complex cells in biology. Their intricate geometry presents many challenges for cell function, in particular with regards to the efficient trafficking of newly synthesized proteins from the cell body or soma to distant locations on the axon or dendrites. In healthy cells, the regulation of protein trafficking within a neuron provides an important mechanism for modifying the strength of synaptic connections between neurons, and synaptic plasticity is generally believed to be the cellular substrate of learning and memory. On the other hand, various types of dysfunction in protein trafficking appear to be a major contributory factor to a number of neurodegenerative diseases associated with memory loss including Alzheimer?s. This project involves the mathematical modeling and analysis of one important aspect of protein trafficking, namely, the transportation of glutamate receptors in dendrites. These receptors mediate the majority of excitatory synaptic transmission in the central nervous system, and changes in the number of synaptic glutamate receptors contribute to the most studied forms of synaptic plasticity, namely, long term potentiation and depression (LTP and LTD). Building upon recent work of the PI, the research will consider a novel reaction-diffusion model of receptor trafficking that combines diffusion along the surface membrane of the cell membrane with biochemical processes within individual synapses. This mathematical model will be used to investigate the regulatory mechanisms that control the distribution of glutamate receptors along a dendrite under basal conditions, during synaptic plasticity and during neurodegeneration. A quantitative understanding of these regulatory mechanisms could help to identify important molecular and cellular processes underlying learning and memory in healthy brains, as well as memory-loss in diseased brains. The work will have a broader impact through its interdisciplinary training of graduate students and through the University of Utah?s Brain Institute, which plays a major educational role in promoting awareness and understanding within the local community.