Margaret Bidwell Memorial Lecture: Synapses lost and found: Developmental critical periods and Alzheimer’s disease
Description
The brain is the most incredible computational machine imaginable. There are over one trillion nerve cells in the brain, and each cell can make 10,000 synaptic connections with other nerve cells. How are connections wired up during development? The wiring problem is solved sequentially first by forming a basic scaffold of connectivity according to genetic blueprints: strict molecular cues enable growing nerve connections to follow appropriate pathways to their correct target regions. Then, once this basic scaffold of connectivity forms, the exact details of each circuit emerge by pruning and sculpting synapses from the immature pattern of connections. The decision-making process that determines which synaptic connections remain and which are pruned is also genetically specified but in this case requires brain function. Even before birth, the brain generates its own internal neural activity patterns to jump-start the sculpting process. After birth once sensory systems, such as the eyes and ears, become mature enough, experience of the external world takes over to influence brain wiring during developmental critical periods. Neural activity and sensory experience regulate the expression of sets of genes including several previously thought to act only in the immune system. These activity-regulated genes- including Major Histocompatibility Class I family members and Paired immunoglobulin-like receptor B- are required in neurons for pruning and sculpting synapses during development. Unexpectedly, they may also contribute to excessive synapse pruning in Alzheimer’s disease. Thus, the baby's brain is not a miniature version of the adult, but rather is a dynamically changing structure in which neural activity and experience ultimately select and stabilize essential details of neural circuitry that make each of us different from one another.
Speaker Bio
Dr. Shatz’s research aims to understand how early developing brain circuits are transformed into adult connections during critical periods of development. Her work, which focuses on the development of the mammalian visual system, 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 graduated from Radcliffe College in 1969 with a B.A. in Chemistry. She was honored with a Marshall Scholarship to study at University College London, where she received an M.Phil. in Physiology in 1971. In 1976, she received a Ph.D. in Neurobiology from Harvard Medical School, where she studied with Nobel Laureates David Hubel and Torsten Wiesel. During this period, she was appointed as a Harvard Junior Fellow. From 1976 to 1978 she obtained postdoctoral training with Dr. Pasko Rakic in the Department of Neuroscience, Harvard Medical School. In 1978, Dr. Shatz moved to Stanford University, where she attained the rank of Professor of Neurobiology in 1989. In 1992, she moved her laboratory to the University of California, Berkeley, where she was Professor of Neurobiology and an Investigator of the Howard Hughes Medical Institute. From 2000-2007 she was Chair of the Department of Neurobiology at Harvard Medical School and the Nathan Marsh Pusey Professor of Neurobiology. Dr. Shatz has received many awards including the Gill Prize in Neuroscience in 2006. In 1992, she was elected to the American Academy of Arts and Sciences, in 1995 to the National Academy of Sciences, in 1997 to the American Philosophical Society, in 1999 to the Institute of Medicine, and in 2011 she was elected as a Foreign Member of the Royal Society of London. Dr. Shatz was awarded the Gerard Prize in Neuroscience from the 40,000 member Society for Neuroscience, and in 2015, the Gruber Prize in Neuroscience. In 2016, she was the recipient of the Champalimaud Vision Prize, and the Kavli Prize in Neuroscience for the discovery of mechanisms that allow experience and neural activity to remodel brain circuits. Most recently (2018) she received the Harvey Prize in Science and Technology from the Technion Israel Institute of Technology.
Additional Info
The annual Margaret Bidwell Memorial Lecture brings BCS community together to learn more about brain diseases and disorders. The lecture, part of the MIT Colloquium on the Brain and Cognition series, was made possible by a gift established in 1997 by John B. Bidwell (MIT SB 1963, MCP 1966), in honor of his late wife.
“John was very connected to the educational mission of the Institute,” says Prof. Mriganka Sur, Newton Professor of Neuroscience and Director of the Simons Center for the Social Brain, who oversaw the gift during his time as Department Head of BCS. “He tapped into his life savings to establish this lecture as a heartfelt way to remember his beloved wife’s legacy. It is a shining example of the impact that gifts of all sizes can have on the department”
In the early 1950s, Margaret was a widowed single mother of two young children working at the Hingham Ammunitions Depot, a local naval base. John was stationed there as an active member in the Navy, where he eventually attained the rank of captain. According to John’s stepchildren Edward Donlon and Mary Gegler, the couple “balanced each other beautifully.” Margaret and John married in 1960.
Throughout his life, John fostered a deep connection to MIT and a lifelong love of learning. He had earned his first Bachelor’s degree from Harvard University in 1954, and later attended MIT, earning a second Bachelor’s degree in economics and a Master’s degree in urban planning. John stayed on at MIT after his graduate studies, working in the urban planning department until his retirement in 1998.
“My mother was so supportive of John’s desire to further his education,” remembers Gegler. “Sometimes he would lose track of time, studying on campus until late into the night. My mother would drive to Cambridge from our home in Milton to pick him up, no matter how late it was.”
In 1981, Margaret was diagnosed with amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease that impacts the neurons that control muscle movement. As her health declined, John became her primary caretaker and advocate until her death in 1983. After years of careful research, John decided how he wanted to memorialize his wife as he neared retirement. John and his family had witnessed the cognitive impact that ALS had on Margaret. John wanted his gift to support basic science research in the area of brain disorders, which is how he ultimately selected BCS to receive his gift. And that’s when he approached Sur in BCS.
“We discussed options for his gift to the department, and I suggested a lecture series centered on brain disorders and diseases endowed in his wife’s name,” says Sur. “We don’t have a medical school at MIT, but we are basic scientists with a deep connection to these diseases, and this was our first focused effort to bring our faculty and students together with experts in the field of brain disorders. It paved the way for some of our most successful initiatives, like the Simons Center for the Social Brain and the MIT Aging Brain Initiative.”
John attended the lectures until his death in 2017. Donlon and Gegler have continued the family tradition by attending the lecture as their schedules allow, and each year they are blown away by the scope of the event, noting their appreciation that John created a meaningful lasting memory of their mother.
“John’s love for MIT was boundless, and he felt confident that the research and community and that it was the best way to establish a lasting legacy in our mother’s legacy,” says Donlon. “While we aren’t scientists ourselves and may not understand the topics of the lectures, the important thing is that someone in the audience does, and the impact of that is enormous. It really was a perfect act of love for our family that upholds John’s belief that you could enrich your life through education.”