Assistant Professor, Department of Pathology and Cell Biology in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Department of Neuroscience, Columbia Translational Neuroscience Initiative, Columbia University
Abstract: Brain circuits can be structurally rearranged with experience, and synaptic connections can grow and be eliminated, even in adults. Dendritic spines are highly dynamic structures whose morphology and lifespan are modified as a response to synaptic efficacy changes between neurons. In order to understand how activity influences synaptic structure and function, we combine the precise stimulation of defined inputs using two-photon glutamate uncaging with whole cell electrophysiological recordings and imaging. We show that activity at specific inputs can lead to the production of new proteins, promoting bidirectional, long lasting plasticity of single spines, as well as cooperation and competition between multiple co-active synapses. Based on this, we predict that synaptic competition for newly made proteins constrains the number of inputs that can undergo structural changes during activity, a process that may become dysregulated in neurodevelopmental disorders with dysregulated proteostasis. We are determining with high precision whether abnormal synaptic competition contributes to altered micro-circuitry in Fragile X Syndrome, and consider whether this represents a core mechanism of dysfunction across Autism Spectrum Disorders (ASDs). Our goal is to gain an understanding of how diverse forms of activity drive spine interactions, and how these processes influence the refinement of local neural circuits both in health and disease.