Brain circuits are highly complex and require carefully executed developmental programs for proper connectivity and function. Not surprisingly, genetic and physical insults during development cause a wide range of neurological conditions that affect complex functions such as sensation, movement and cognition or disrupt other fundamental behaviors such as breathing, feeding, or sleeping.
The ultimate goal of the work in the Sillitoe lab is to uncover the developmental origins of complex neurological conditions. Dr. Sillitoe has a long standing interest in using the cerebellar branch of the motor system as a model for understanding brain development and disease. The cerebellum is well-known for its roles in controlling motor coordination, motor learning, and balance. However, there is accumulating evidence that the cerebellum also participates in cognition and emotion. It is therefore not surprising that defects in the cerebellum are thought to contribute to a number of devastating neurological disorders including ataxia, dystonia, autism spectrum disorders, and obsessive-compulsive disorder.
As a model, the cerebellum is experimentally tractable because it has an exquisitely organized architecture and well-understood circuit connections. The Sillitoe research team exploits these characteristics to study how genes and neural activity interact to establish functional neural circuits that control complex behaviors. For their studies, the Sillitoe group uses an interdisciplinary approach that combines sophisticated mouse molecular genetics with high-resolution neuroanatomy and in vivo electrophysiology. For example, by altering the expression and function of the engrailed homeobox genes Dr. Sillitoe has found that cerebellar patterning cues control the precise targeting of excitatory and inhibitory connections that are required for smooth purposeful movements.
The immediate goal of the lab is to determine the developmental mechanisms that are affected after disrupting the functions of disease-linked genes. The hope is that in the long-term, the mechanisms they reveal will shed light on the causes of brain disease and perhaps offer novel therapeutic targets to improve the quality of life in affected individuals.