Date: Wednesday, October 8, 2025
Location: 46-3002 (Singleton Auditorium)

Speaker: Carla J. Shatz, Ph.D.
Affiliation: Professor of Biology and Neurobiology, Stanford University

Host: Dr. Mriganka Sur

Talk title: Surprise at the Synapse: classically immune genes in neurons and synapse pruning

Abstract:
Carla J. Shatz and her lab, Bio-X, Departments of Biology and Neurobiology, Stanford University

During brain development, circuits form sequentially, first by creating a basic scaffold of connectivity according to strict molecular axon guidance cues. Subsequently final details of each circuit emerge by pruning and sculpting synapses. This synapse selection process is also genetically specified but in contrast to axon guidance, the program requires neural activity. Prenatally even before vision the brain generates its own internal neural activity patterns- in the form of spontaneous retinal waves- to jump-start the sculpting process. Postnatally, visual experience takes over to sharpen brain wiring during critical periods. Neural activity and sensory experience regulate expression of sets of genes including several previously thought to act only in the immune system. These genes- including Major Histocompatibility Class I family members and the MHCI receptor Paired immunoglobulin-like receptor B- are required in neurons for pruning and sculpting synapses during development. In human cerebral cortex, MHCI proteins (= HLA class I) and LilrB2 (a PirB homolog) are expressed at excitatory synapses where, by analogy, they may also collaborate in synapse pruning. Neurons in human cortical organoids express these molecules and in an in vitro model of maternal immune activation, exposure to inflammatory cytokines results in a striking increase in neuronal expression of HLAI family members, as well as in altered patterns of spontaneous neural activity. It is possible that changes in expression and/or function of these molecules in the brain lead to alterations in synapse pruning that could underlie developmental disorders. In SFARI Gene, LilrB2 and several HLA class I genes are categorized as "strong" ASD candidates, with statements that these genes contribute solely to immune system dysfunction. In view of the observations above, a neuronal function for these genes merits further study. Supported by NIH EY02858, NIA AG065206, Mathers Charitable Foundation, Sapp Family Foundation, Phil and Penny Knight Stanford Initiative for Brain Resilience.

Bio: Carla J. Shatz is Sapp Family Provostial Professor of Biology and Neurobiology and the Director Emerita of Bio-X, Stanford University’s pioneering interdisciplinary biosciences program. She received her B.A. in Chemistry from Harvard University (Radcliffe College) in 1969 and then an M.Phil. (Physiology; 1971) from University College London on a Marshall Scholarship. In 1976 she received her Ph.D. in Neurobiology from Harvard Medical School, mentored by David Hubel and Torsten Wiesel. Shatz joined the faculty at Stanford in 1978, then moved to University of California Berkeley in 1992, and to Harvard Medical School in 2000 as the first woman to Chair the Department of Neurobiology. She returned to Stanford in 2007 to direct Bio-X. Dr. Shatz is a neuroscientist who has devoted her career to understanding the dynamic interplay between genes and environment that shapes brain circuits - the very essence of our being. Shatz has earned many honors and awards, including election to the National Academy of Sciences, the American Philosophical Society and the Royal Society of London. She received the Gruber Neuroscience Prize in 2015. In 2016, she was the recipient of the Champalimaud Vision Prize, as well as 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 from the Technion Israel Institute of Technology.