Burdon Sanderson Prize lecture: Synaptic plasticity, calcium regulation and Alzheimer’s disease
Followed by a reception in the Sherrington foyer.
Homeostatic regulation of synapses is vital for healthy nervous system function. Activity-dependent synaptic scaling, an intensely studied form of homeostasis, is proposed to operate over hours to counteract the destabilizing influence of long-term potentiation (LTP) and long-term depression (LTD). The prevailing view holds that synaptic scaling is a slow first-order process that regulates postsynaptic glutamate receptors and fundamentally differs from LTP or LTD. Our experiments challenge these presumptions. Surprisingly, the dynamics of scaling induced by neuronal inactivity are not exponential or monotonic and the mechanism requires calcineurin and CaMKII, molecules dominant in LTD and LTP. Our quantitative model of the interplay between these enzymes reconstructs the unexpected dynamics of homeostatic scaling and reveals how synapses efficiently safeguard future capacity for synaptic plasticity on demand. The modeling also provides a framework for understanding Alzheimer’s disease and how calcium dysregulation in AD might cause disruption of synaptic homeostasis. Our human genetics-based experiments in mouse models of Alzheimer’s implicate this kind of pathophysiological connection.
Date: 17 October 2022, 16:00 (Monday, 2nd week, Michaelmas 2022)
Venue: Sherrington Building, off Parks Road OX1 3PT
Venue Details: Blakemore Lecture Theatre
Speaker: Richard W. Tsien (Druckenmiller Professor of Neuroscience, Chair of the Department of Physiology and Neuroscience, and Director of the NYU Neuroscience Institute at New York University Medical Center)
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organiser: Professor David Paterson (DPAG, University of Oxford)
Organiser contact email address: hod-pa@dpag.ox.ac.uk
Host: Professor David Paterson (DPAG, University of Oxford)
Part of: Burdon Sanderson Cardiac Science Centre Lecture
Booking required?: Not required
Audience: Members of the University only
Editor: Talitha Smith