How are connections wired up during brain development? Wiring occurs sequentially, first by forming a basic scaffold of connectivity according to strict molecular guidance cues. Subsequently the exact details of each circuit emerge by pruning and sculpting synapses. This synapse selection process is also genetically specified, but in this case requires brain function. Prenatally, the brain generates its own internal neural activity patterns to jump-start the sculpting process. Postnatally, experience of the external world takes over to influence brain wiring during developmental 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 activity-regulated genes, including Major Histocompatibility Class I family members and Paired immunoglobulin-like receptor B (PirB), are required in cortical and hippocampal neurons for synapse pruning and plasticity. Unexpectedly, PirB also acts as a high affinity receptor for soluble oligomers of beta amyloid and contributes to cognitive loss and alterations in Hebbian synaptic plasticity in mouse models of Alzheimer’s disease. Changes in expression or function of these molecules could contribute to synapse pruning disorders in development such as Schizophrenia, as well as in neurodegenerative disease.
Carla J. Shatz is Sapp Family Provostial Professor of Biology and Neurobiology and the Catherine Holman Johnson Director of Bio-X, Stanford University’s pioneering interdisciplinary biosciences program. She received her B.A. in Chemistry from Radcliffe College in 1969, an M.Phil. (Physiology; 1971) from University College London as a Marshall Scholar, and a Ph.D. (Neurobiology; 1976) from Harvard Medical School. Shatz joined the faculty at Stanford in 1978, then moved to University of California at Berkeley in 1992, and to Harvard Medical School in 2000 as the first woman Chair of 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, and also 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.