"Proper functioning of the brain requires points of rapid communication between nerve cells. This is achieved at specialized junctions called chemical synapses, which function by the vesicular release of neurotransmitter onto a post-synaptic apposition decorated with neurotransmitter-gated ion channels. Fast chemical synapses release glutamate to activate AMPA-type glutamate receptor ion channels, which excite the post-synaptic neuron. Since these receptors desensitize rapidly, their dynamic exchange with naïve extrasynaptic receptors by surface diffusion plays an important role in shaping the short-term plasticity of synapses and thus the fidelity of synaptic transmission. Localized glutamate transients in the synaptic cleft and the gating kinetics of AMPA receptors occur on the millisecond timescale. Furthermore, the steep glutamate concentration gradients lead to heterogeneous binding-site occupancy and receptor gating. Therefore, the position of vesicle release locations relative to AMPA receptor confinement and diffusion are of crucial importance to understanding the fundamental operating principles of excitatory synapses. Therefore, this project proposes new super-resolution methods for simultaneous live-cell imaging of individual vesicle release events and synaptic AMPA receptor confinement and diffusion. Within this context, the project will also investigate a role in short-term plasticity for multiple release locations and the diffusional exchange of low-occupancy AMPA receptors at the synapse."
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