Stories of Women in Neuroscience · Stories of WiN

Dr. Carla Shatz

·1 hr 3 min·3 clips

Blocking abnormal brain pruning may prevent Alzheimer's cognitive decline

Dr. Carla Shatz discusses her pioneering research on how brain circuits develop and change, and how these insights connect to neurodegenerative diseases like Alzheimer's. Host Nancy Padilla interviews Shatz, a Stanford professor and former president of the Society for Neuroscience, who has received the Gruber and Kavli prizes. Shatz began her career as an undergraduate at Radcliffe College, where she developed a passion for vision science through her dual interests in art and biology. Her chemistry advisor connected her with David Hubel and Torsten Wiesel, who were conducting their Nobel Prize-winning research on the visual cortex at Harvard Medical School. As their first undergraduate researcher, Shatz was captivated by their discoveries of ocular dominance and orientation columns in the visual system. Her graduate thesis investigated the miswired visual system of Siamese cats, a genetic model that revealed how developmental errors affect brain connections. For her postdoctoral work, she trained with Pasko Rakic to study embryonic brain development, learning techniques to examine the nervous system before birth. Shatz's own lab made the landmark discovery that precise connections from the eye to the brain are not hardwired but emerge through activity-dependent remodeling before vision begins. She and her team found that spontaneous, wave-like neural activity in the developing retina—not visual experience—guides this wiring process. Using multi-electrode arrays and later calcium imaging, they visualized these "retinal waves," which many in the field initially dismissed as an artifact. The waves are generated by an early circuit of retinal ganglion cells and amacrine cells, demonstrating the brain's intrinsic drive to create correlated activity. Shatz coined the phrase "fire together, wire together" to describe how this synchronous activity strengthens appropriate connections via Hebbian plasticity. Her research later revealed that immune system molecules, like MHC class I proteins, are crucial for the synaptic pruning that refines these neural circuits during development. This finding unexpectedly connected her developmental work to Alzheimer's disease, where excessive "unsupervised pruning" may contribute to cognitive decline. In mouse models of Alzheimer's, blocking a pruning receptor called PirB protected the mice from cognitive deficits despite high levels of beta-amyloid. Shatz expresses deep concern about declining federal funding for basic, discovery-based research, which enabled her own high-risk studies. She reflects on being the first woman to earn a Ph.D. from Harvard's neurobiology department and later its first female chair, initially admitted as an "experiment" because some faculty doubted women would remain in science. The episode maintains an educational and conversational tone, blending detailed scientific explanation with personal narrative and historical context. Listeners interested in brain development, the history of neuroscience, or the surprising links between neural wiring and disease will find this episode compelling. Those seeking a purely clinical discussion of Alzheimer's or a fast-paced narrative might find the detailed basic science segments less engaging.

As heard by us

A thoughtful career portrait connecting art, early neural activity, and the Hebb-like synapses behind a memorable teaching phrase.

Dr. Carla Schatz's story begins with a love of science and art at Radcliffe College, Harvard, at a time when, as she recalls, there was no neuroscience. From there, the episode follows her into a career spent studying how brain circuits change with experience.

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Want to hear how spontaneous brain activity helps early brain circuits find their shape? This is your kind of science story.

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