Presynaptic Regulation of Release and Spread of Glutamate in CN

University Of Iowa, Iowa City IA

Investigators

Abstract

Glutamate is a major excitatory neurotransmitter in the brain, whose concentration in the space between two communicating neurons results from the fusion of synaptic vesicles (specialized compartments that serve as neurotransmitter repositories) with the cell membrane of the signaling neuron. This concentration plays an important role in both physiological and pathological processes because it affects the response amplitudes (quantal sizes), and is thus tightly regulated through various mechanisms. It was recently proposed that the mode of vesicle release from the signaling neuron may serve as a physiological determinant of the rapidity of glutamate secretion. According to a classical hypothesis, a vesicle collapses completely at the membrane of the signaling neuron, leading to rapid secretion of its total glutamate content into the extracellular space. In contrast, according to a newly proposed hypothesis, a vesicle can maintain its shape while secreting glutamate through a narrow channel, leading to more measured secretion. However, the validity of the new concept and its effect on the extracellular glutamate concentration are not well substantiated. The proposed study will investigate the causative link between a particular mode of vesicle fusion and the resulting glutamate concentration, using an innovative optical monitoring system. The investigators expect to find such link and its modulation under various conditions. The results of the study will shed light not only on the spatial and temporal aspects of synaptic transmission, but also on the robustness, adaptability and resilience of neurotransmission. Furthermore, they are likely to lead to important insights into glutamate-dependent cognitive processes, such as the formation and maintenance of memory. The investigators will also be dedicated to the training of pre-college, undergraduate and graduate students in analytical thinking, through outreach activities on general science and discussion of synaptic physiology in classes or laboratories.