Carla J. Shatz, the 2016 Kavli Prize laureate in neuroscience who discovered how a set of molecules in the immune system might be the key to protecting against memory loss in Alzheimer’s disease, will deliver the next Virginia Tech Carilion Research Institute Maury Strauss Distinguished Public Lecture at 5:30 p.m. on Thursday, Nov. 29. Her talk, titled, “Synapses Lost and Found: Developmental Critical Periods and Alzheimer’s Disease,” will take place at 2 Riverside Circle in Roanoke, Virginia.
Shatz is the Sapp Family Provostial Professor at Stanford University, where she also serves as the David Starr Jordan Director of Stanford Bio-X, a translational accelerator dedicated to benefiting human health through the kind of cross-disciplinary research that led Shatz to uncover a potential therapeutic target for a major psychiatric disorder.
“Connections in the adult brain are precise, but they do not start out that way,” said Shatz, who is an elected member of the National Academy of Sciences. “Precision emerges during developmental critical periods as synapses – the delicate contacts between neurons that relay and store information – are either pruned away or grow in a process driven by learning.”
The brain doesn’t wait to wire itself, according to Shatz. She compares it to a fetus kicking in the womb. The baby is practicing movements it will need later on. As the baby grows into a toddler who runs, the leg muscles become stronger. The same thing happens with synapses in the brain. As learning encourages certain connections, those pathways become stronger, while lesser-used connections fade away.
While studying which genes might influence this synaptic plasticity in the brain’s visual system, Shatz discovered that Major Histocompatibility Complex (MHC) molecules – known for their role in helping the body’s immune system fight infection – were heavily involved in brain’s ability to remodel. She also found the brain contained significantly more synaptic connections in a mouse model with fewer MHC molecules.
Shatz determined that MHC molecules send a kind of synaptic shearing signal through a receptor on neurons. By blocking the function of these molecules, Shatz found that a critical period for vision can be reopened in the adult mouse brain. She also demonstrated that the same receptor binds with the amyloid plaques that accumulate in Alzheimer’s disease. The same functional blocking that allows for more synaptic connections in the visual systems also helps protect against memory loss in a mouse model of Alzheimer’s disease. Now, she’s exploring new avenues for treating developmental disorders and Alzheimer’s disease by better understanding the function of these molecules in the brain.
“Dr. Shatz has made multiple major contributions to our understanding of the dynamic interplay between genes and environment and how they contribute to shaping brain circuits,” said Michael J. Friedlander, executive director of the VTCRI and Virginia Tech’s vice president for Health Sciences and Technology. “Her ongoing studies of molecular mechanisms have revealed a role for entirely unexpected genes – those that are essential for immune recognition, being expressed at neuronal synapses. These findings are relevant not only for understanding the development of normal brain wiring and how the nervous system and immune system interact but also for understanding developmental disorders such as autism and schizophrenia.
“Dr. Shatz’s discoveries have revealed new mechanisms for neural development and for Alzheimer’s disease, opening up new strategies for treatment, contributing to the emerging view that the intersection between neural and immune systems underlies epigenetic mechanisms of neurological and psychiatric disorders,” Friedlander said.
Shatz earned her doctorate degree in neurobiology from Harvard Medical School – the first woman to do so – under the mentorship of Nobel Laureates David Hubel and Torsten Wiesel, where she was also appointed a Harvard Junior Fellow. After completing her postdoctoral training at Harvard, Shatz joined the faculty at Stanford University before moving to the University of California, Berkley, where she served as a professor and an Investigator of the Howard Hughes Medical Institute. She returned to the East Coast to chair the Department of Neurobiology and serve as the Nathan Marsh Pusey Professor of Neurobiology at Harvard Medical School. She assumed her current positions at Stanford University in 2007.
Shatz is an elected member of the American Academy of Arts and Sciences; of the American Philosophical Society; of the Institute of Medicine; and as a Foreign Member of the Royal Society of London. Shatz has been awarded the Gill Prize in Neuroscience, the Society for Neuroscience’s Gerard Prize in Neuroscience, and 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. In 2018, she received the Harvey Prize in Science and Technology.
The lecture is free and open to the public. A reception will precede the talk at 5 p.m.