SCSB Colloquium Series with Dr. Carla J. Shatz: Surprise at the Synapse: classically immune genes in neurons and synapse pruning

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.