Date(s) - 08/15/2014
8:00 pm - 9:00 pm
Friday Evening Lecture Series – “Surprise at the Synapse: Developmental Critical Periods and Alzheimer’s Disease – Can Knowledge of One Help Cure the Other?”
Carla Shatz, Stanford University
August 15, 2014, 8:00 PM, Lillie Auditorium
Introduction by Dr. Joan Ruderman, President and Director, MBL
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.
Dr. Carla Shatz is the Sapp Family Provostial Professor of Biology and Neurobiology and Director of Bio-X at Stanford University. The interdisciplinary biosciences program unites engineering, computer science, physics, and chemistry with traditional biology and medicine to study the complexity and find solutions to critical problems of the human body. Her research is focused on understanding the dynamic interplay between genes and environment that shapes brain circuits.
Dr. Shatz received her B.A. in Chemistry from Radcliffe College and was the first woman to earn a Ph.D. in neurobiology from Harvard Medical School. During her years in graduate school, Dr. Shatz worked with David Hubel and Torsten Wiesel, who later went on to win, with Roger Sperry, the Nobel Prize in Physiology or Medicine. Dr. Shatz is one of the pioneers who determined some of the basic principles of early brain development, and her research on the cellular and molecular mechanisms of how the early 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 how the nervous and immune systems interact.
Dr. Shatz has served as President of the 40,000-member Society for Neuroscience. She is a former member of MBL’s Science Council. Dr. Shatz has received many awards and honors including election to the National Academy of Sciences and the Royal Society of London as a Foreign Member. She has earned the Salpeter Lifetime Achievement award from the Society for Neuroscience and the Ralph W. Gerard Prize, both for significant career achievements in neuroscience. Most recently, she received the Sackler Prize for Distinguished Achievement in Developmental Psychobiology and the Pasarow Foundation Award in Neuropsychiatry Research.