Sarah Ackerman, PhD

Assistant Professor, WashU Pathology & Immunology

Understanding how glia shape developmental and pathological plasticity

Organismal behavior, from simple to complex, is dependent on the faithful wiring of neurons into functional neural circuits. Because stereotyped circuit output is required for predictable behavior, it is easy to hypothesize that neural circuits would be hardwired from development. Nonetheless, neural circuits undergo dramatic experience-dependent remodeling during brief developmental windows called critical periods, which show unique temporal profiles across distinct neural circuits. Mature circuits, by contrast, show relative stability in structure/function. Although altered critical period timing is linked to neurodevelopmental disorders, the mechanisms that set critical period timing and maintain mature circuit stability remain poorly defined. Our goal is to define the ON/OFF switches for neural circuit plasticity. We recently identified astrocytes, the most abundant glial cell type in the brain, as essential brakes on neural plasticity. We found that loss of astrocytes, or of astrocyte-derived cues, results in extension of critical period plasticity and life-long changes in organismal behavior. The Ackerman lab asks how developmental plasticity informs long-term circuit stability and physiology. Furthermore, we leverage astrocytes to tune plasticity in conditions where too much (e.g. neurodegeneration) or too little plasticity (regeneration) is detrimental to human health. By using two model systems, zebrafish and Drosophila, we aim to identify conserved cellular and molecular mechanisms that stabilize neural circuits in vivo, from flies to humans. These goals are directly related to the mission of the Hope Center: understanding fundamental mechanisms that contribute to the development of neurological disorders and devising innovative strategies to improve human health.

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