Seminar "Nanostructure and alignment control function of single synapses" by Prof. Thomas Blanpied

Title: Nanostructure and alignment control function of single synapses

Speaker: Prof. Thomas Blanpied from University of Maryland, School of Medicine

Abstract:

Plasticity of synaptic function arises from a combination of altering the protein content and molecular organization of individual contact sites. Recent work from many types of glutamatergic synapses has made clear that both presynaptic and postsynaptic function arise from precise organization of key molecular species within subsynaptic ensembles tens of nanometers in diameter. In the postsynaptic density, clustered scaffolding proteins create subdomains enriched in AMPA and NMDA receptors. We find that RIM and other key proteins that regulate vesicle fusion are mutually co-enriched within subregions of the AZ. By mapping sites of single-vesicle fusion events within individual AZs, we revealed that evoked fusion occurs in a confined subregion of the AZ where RIM density is highest. Remarkably, dSTORM showed that in hippocampal neurons in culture or in brain slices, the distributions of RIM and receptors are highly co-aligned across the synaptic cleft. Numerical modeling indicates that this simple organizational principle provides a means by which CNS synapses can maintain and modulate synaptic efficiency. Because numerous forms of synaptic plasticity are executed by the dense and dynamic spine actin cytoskeleton, we explored whether manipulation of actin filaments alters trans-synaptic alignment. Treatment of neuron cultures with latrunculin indeed strongly altered measures of nanoscale alignment, notably decreasing the concentration of presynaptic RIM in close registration with nanoclusters of postsynaptic PSD-95. This suggests that activity-dependent regulation of cytoskeleton may dynamically tune synaptic function via controlled transsynaptic alignment.

Biography:

I graduated from Yale University with a bachelor’s degree in Psychology. My long-standing interest in cognition and learning has lead to my current work to understand the cellular processes that underlie mental health and psychiatric disorder. At the University of Pittsburgh, I obtained a Ph.D. in the Department of Neuroscience with Jon Johnson, Ph.D., where I used single-channel recordings to study the mechanisms by which the anti-Parkinsonian and anti-Alzheimer’s drugs amantadine and memantine act on NMDA receptors. I then undertook postdoctoral training with George Augustine, Ph.D. and Michael Ehlers, M.D. Ph.D. at Duke University in the Department of Neurobiology, with whom I studied the cell biological mechanisms of synaptic transmission and neural plasticity. I joined the University of Maryland Department of Physiology as an Assistant Professor in 2005, and became Associate Professor with tenure in 2012.