BMI Seminar // Molecular architecture of synapses in situ by cryo-electron tomography

Understanding synaptic structure, function, connectivity and plasticity is fundamental to understanding how the brain works. Synaptic plasticity is fundamental for learning and memory formation where neurons are able to shape their length, structure and distribution of synapses thus accommodating local synaptic activity. Under pathological conditions such as Alzheimer’s disease, uncontrolled large-scale loss of synapses triggers local neural degeneration. We use a variety of advanced biophysical techniques to study the structure, the function and plasticity of synapses. These include sample cryopreservation, and cryo- electron microscopy and tomography of specimens from mouse models, cultured cells or primary cell lines and correlative light and electron microscopy and tomography. In my talk, I will show the detailed analysis of the three-dimensional molecular architecture of presynaptic active zones of specific type of synapses and how they function. This study will open possibilities, using these advanced techniques, to investigate the synaptic structural plasticity in normal aging as well as in neural disorder and age-related dementia (e.g. Alzheimer model disease) and to understand the molecular mechanism of neurodegenerative diseases.