A Hobbit's Guide to Neurodevelopment; An Unexpected Journey into the Innate

Abstract

Brain development presents a remarkable case of biological self-assembly: the intricate, yet reproducible, circuitry of our mind arises from a tapestry of local cell decisions. Similar processes are ubiquitous across tissues, suggesting that distilling this complexity into simple, yet predictive models, offers valuable avenues to understand and manipulate development. Utilizing a blend of data analytics, computational simulations, and empirical studies, I explore the role of a cell's genetic makeup in shaping its synaptic connections. I first show that the genetic recognition rules governing neuronal wiring can be systematically extracted from a cell’s (1) connectivity, (2) gene expression, and (3) physical contacts (Chapters 1 and 2). Next, I illustrate how such simple neuronal recognition rules provide sufficient information to even hardwire a human brain, with additional specific results on encoding complex networks that perform competitively on ML benchmarks (Chapters 3 and 4). Finally, I show that Development, not Attention, is all you need: by raising zebrafish under anesthesia, I show that circuits underlying complex sensory behaviors can be wired up with no learning at all, simply by activity-independent developmental mechanisms (Chapter 5). In summary, by marrying network science, neurodevelopment, and artificial intelligence, I offer a fresh, quantitative lens on the enduring debate of nature versus nurture, leaning decisively towards the primacy of innate developmental processes over learned behavior.