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Shasta Sabo, Ph.D.

Assistant Professor

Phone: (216) 368-5683
Fax: (216) 368-1300
E-mail: shasta.sabo@case.edu
W343B Wood Building

Laboratory

Research

Nature versus nurture: this phrase represents one of the most fundamental and long-debated questions in neuroscience. While it is clear that experience and environmental cues (nurture) modulate the framework established by genetic programs (nature) to create our personalities and patterns of behavior, the molecular and cellular mechanisms by which genes and environment interact remain incompletely understood.
Neuronal circuits in the brain are the neural substrate for behavior and perception, and neuronal activity is the neural correlate of experience. In order to fully understand how “nurture” modulates what “nature” gives us, we must understand how neuronal activity influences development of our brain circuitry. One of the best studied areas in the central nervous system with regard to the role of activity in neural development is the visual cortex. Therefore, we primarily study the mechanisms that establish neural circuits within the visual cortex. We are also interested in comparing synapse formation in sensory and frontal cortices.
Synapse formation is one of the most important steps during assembly of the neural circuits that control perception and behavior. This represents an enormous and complex task: in babies and children roughly 10-20 billion neurons that comprise the cerebral cortex must form trillions of synapses. Importantly, synapse assembly is probably also the stage at which the role of activity in shaping neural circuitry is most poorly understood. For these reasons, our research focuses on how synapse formation is controlled by the interaction of genes and activity.
In addition to being one of the most fascinating issues in neuroscience, understanding the mechanisms of synapse and circuit formation has vast translational relevance. Devastating diseases --including autism, mental retardation, epilepsy, amblyopia, anxiety disorders, depression and schizophrenia-- are linked to abnormal circuit development. Understanding the choreography of synaptogenesis is essential for understanding the etiology of such diseases. Synaptogenesis is also important for repair after brain injury, integration of stem cell-derived neurons into neuronal networks, and treatment of disorders like Alzheimer’s Disease in which synapse loss occurs prior to diagnosis.

To truly understand how genes and activity interact to control synapse formation, we must establish a detailed understanding of the sequence of events that occurs during synapse formation. Despite this, the cellular mechanisms of CNS synapse assembly remain surprisingly unclear, especially for presynaptic terminals. To create the foundation for future work on the molecular mechanisms that control synapse formation, we have been undertaking studies to define the cellular mechanisms of synapse formation. For example, we are currently working to understand how the protein complexes and specialized membrane domains critical for synaptic transmission assembled at the right place at the right time.
To study synapse formation, we use live fluorescence confocal imaging to study individual synapses and networks in real-time, as they form. This approach permits us to use both genetic and pharmacological tools to manipulate the expression and function of individual proteins during synaptogenesis. We complement our imaging studies with electrophysiological approaches to investigate synapse and local circuit function.