Synapses lost and found: developmental critical periods and Alzheimer’s disease - Carla Shatz

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Thursday, October 9, 2014
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4:15pm to 5:00pm PDT
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Carla Shatz, PhD

Sapp Family Provostial Professor of Biology and Neurobiology
David Starr Jordan Director, Bio-X
Stanford University

Synapses lost and found: Development critical periods and Alzheimer's disease

Abstract: Connections in adult brain are highly precise, but they do not start out that way. Precision emerges during developmental critical periods as synaptic connections prune and remodel in a process requiring using your brain (neural activity). Activity also regulates neuronal gene expression. Major Histocompatibility Class I (MHCI) genes –famous for their role in immunity- were unexpectedly discovered to be regulated by vision, and also expressed in neurons, and located at synapses. To assess requirements for MHCI in CNS, mutant mice lacking specific MHCI genes were studied. Synapse pruning in developing visual system fails, and synapse plasticity in visual cortex is greater than normal. In a search for receptors that could interact with neuronal MHCI, the immune receptor PirB was found in mouse brain. In mice lacking PirB, visual system plasticity is also increased and synapse pruning in cortex fails. The commonality of phenotypes present in both types of mutant mice suggests a model in which PirB receptor interacts with MHCI ligands in neurons. Moreover, without PirB, mice do not succumb to the devastating effects of Beta Amyloid- known to be responsible for synapse and memory loss in Alzheimer’s Disease. Together, results imply that these molecules, thought previously to function only in immunity, also act at neuronal synapses to limit how much- or how quickly- synapse strength changes in response to new experience. Changes in their function could contribute to developmental disorders such as Schizophrenia, and even to the synapse loss in Alzheimer’s Disease (Kim et al, 2013).

Bio: Dr. Carla Shatz is Sapp Family Provostial Professor of Biology and Neurobiology and the David Starr Jordan Director of Bio-X, Stanford University’s pioneering interdisciplinary biosciences program that brings together faculty from across the entire university- Clinicians, Biologists, Engineers, Physicists, Computer Scientists- to unlock the secrets of the human body. She received her B.A. in Chemistry from Radcliffe College in 1969, an M.Phil. in Physiology in 1971 from University College London as a Marshall Scholar, and a Ph.D. in Neurobiology from Harvard Medical School in 1976. Dr. Shatz is a neuroscientist who has devoted her research career to understanding the dynamic interplay between genes and environment that shapes brain circuits - the very essence of our being. Her research on cellular and molecular mechanisms of how the early developing brain is transformed into adult circuitry during critical periods of development has relevance not only for treating disorders such as autism and schizophrenia, but also for understanding the synapse loss in Alzheimer’s disease and how nervous and immune systems interact. Dr. Shatz is past president of the 40,000 member Society for Neuroscience; prior to Stanford, she was Chairwoman of the Department of Neurobiology at Harvard Medical School. She has received many awards and honors including election to the National Academy of Sciences, the American Philosophical Society, the Institute of Medicine. In 2011 she was elected as a Foreign Member of the Royal Society of London. Most recently (2013), she received the Sackler Prize for Distinguished Achievement in Developmental Psychobiology and she shared the Robert J. and Claire Pasarow Foundation Award in Neuropsychiatry Research with Karl Deisseroth and Helen Mayberg.