Isabelle Dalle Fusine
Department of Neurobiology, Harvard Medical School
Project Summary: This study will focus on long-term depression (LTD), an important mechanism of synaptic plasticity that modifies synapses in response to neuronal activity and experience. Long-lasting changes in synapse function such LTD are involved in learning and memory and are thought to preclude the pruning of synapses during development. Recent findings indicate that proteins used by immune cells are active in the brain outside the context of neuroinflammatory processes or brain disorders. Caspase-3, an effector of the apoptotic signaling cascade, was recently found to be required for the expression of LTD in hippocampal cells without inducing apoptosis whereas C1q, an effector protein of the complement cascade, mediates the pruning of synapses during development. These studies suggest that LTD and synaptic pruning may be triggered by a local apoptotic-like signaling cascade in central neurons. In order to test this hypothesis I will monitor apoptosis initiation in synapses after LTD induction by visualizing extracellular phosphatidylserine (PS) exposure in dendritic spines of organotypic neuronal cultures using two-photon microscopy.