How developmental noise in neural circuit development determines the unique behavior of individuals

The origins of individual trait variations in a population remain unknown, yet these differences are the very essence of how we function in life and how evolution works.  As an Allen Distinguished Investigator, Bassem Hassan will seek a solution to this long-standing question by studying the role of developmental noise in neural circuit formation. 

In contrast to hard­wired sensorimotor reflexes, such as attraction to food, complex innate behaviors like selective attention show significant variation—even among genetically similar individuals. Rather than being the result of neuromodulation, Hassan’s team has shown that development of these circuits is inherently variable, the result of a dynamic development program that cannot be predicted by genes or environment alone.

This process results in a range of possible neural circuit diagrams among genetically identical individuals. Individuals—whether flies, bees or humans—are known to have distinct “personality” traits, which manifest in behavioral preferences. But how these variations in circuitry actually translate into differences in individual behaviors that remain stable over time is a mystery. Part of the challenge has been identifying a single circuit that can be both analyzed for its differences among individuals as well as linked to a particular behavioral preference.

The Dorsal Cluster Neurons (DCN) in the Drosophila visual system are an ideal environment in which to ask these questions about the link between circuit wiring and behavioral traits. Cells in these circuits show a 30% variability in wiring not only across individuals, but also between the left and right sides of the same brain.

DCNs are essential for a selective attention task, such as fixating on a foreground figure against a noisy, moving background—analogous to crossing the street looking at a fixed destination while monitoring moving traffic.

The neural basis for individual differences in behavior remains an enigma, but is an essential question in neuroscience. In order to understand how and why individuals vary within a population, it is necessary to understand the causal link between the variation in their neural circuitry and their preference for certain behaviors. This research will shed light on this fundamental question, and provide insight into the basis for individual variations in behavior.  This is also the basis by which evolution performs selection of the fittest within a population containing variations, and perhaps maintains variability itself as a population attribute of a given species.

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Affiliated Investigators

Bassem Hassan, Ph.D.

Institut du Cerveau et de la Moelle épinière (ICM)

Bassem Hassan is currently a Team Leader at the ICM in Paris, France. During 2016 the Hassan lab will be transitioning to the ICM from the VIB Institute’s Center for the Biology of Disease and the University of Leuven School of Medicine, in Leuven Belgium, where Bassem is a senior group leader and professor at the faulty of medicine. He obtained his Bachelor of Science degree in Biology at the American University of Beirut, Lebanon, and his Ph.D. in Molecular Genetics at The Ohio State University in 1996. Between 1996 and 2001 he was a Howard Hughes Medical Institute and then an NIH Postdoctoral Fellow at Baylor College of Medicine in Houston, Texas working with Drs. Hugo J. Bellen and Huda Y. Zoghbi on the transcriptional mechanisms of early neurogenesis in Drosophila and mouse. In late 2001 he was recruited to VIB to establish the first Drosophila lab in the country, and in 2016 he was recruited to ICM to establish the laboratory of Brain Development. In 2003 he received the European Molecular Biology Organization (EMBO) Young Investigator award and in 2009 he was elected EMBO member. In 2016 he was named the Einstein Visiting Fellow at the Charité and the Freie Universität Berlin, in Berlin, Germany.

Research in the Hassan lab focuses on understanding the genetic mechanisms that regulate the early development of the nervous system from cell fate specification to neural circuit formation, using Drosophila fruit flies as a model. His research deals with the role that transcriptional regulation and cell-cell signaling shape the identity and connectivity of neurons. Recent work from the Hassan lab has revealed unexpected insights into the quantitative temporal regulation of neuronal cell fate, as well as the role of stochastic processes in brain wiring that challenge previously held assumptions about the emergence of specificity in neural circuit architecture.