Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Barres, Ben A.
Location Stanford University
Primary Field Cellular and Molecular Neuroscience
 Election Citation
Barres has made seminal contributions to understanding interactions between neurons and glia and mechanisms that control synaptic remodeling, including the discovery that thrombospondin and complement proteins function as signals that promote the formation and elimination of synapses, respectively. His work has broad implications for understanding neural development, plasticity, and disease.
 Research Interests
My lab focuses on understanding the role of glia, in particular astrocytes, in the developing, adult, and diseased CNS. We have pioneered the development of methods to purify and culture CNS neuron and glial cell types. Building from these methods, we have found that astrocytes, rather than being passive as long thought, are critical controllers of synapse formation, function, and elimination. We have used molecular biology and biochemistry to identify many of the astrocyte-secreted proteins that control synapse development. More recently we have found that astrocytes are phagocytic, and defined the pathways by which they engulf synapses thereby helping to mediate normal developmental synapse pruning and neural circuit refinement. Astrocytes continue to eat synapses in the adult CNS suggesting that even in the adult brain, synaptic architecture is constantly being actively remodeled by astrocytes. We have also shown that microglia contribute to pruning in response to the activation of the classical complement cascade at developing synapses. Although this complement pathway silences in the adult brain, it reactivates in most neurodegenerative diseases causing the unwanted synapse elimination that drives the progression of these diseases. These findings have two important implications now being investigated in the Barres lab: (1) that compared to mouse, human astrocytes may have evolved to be even better controllers of synapse formation or function providing an astrocytic basis to improved human cognition, and (2) that neurological and psychiatric disorders may be underlied by defects in the ability of astrocytes to control synapses. The Barres lab has also made important contributions to understanding CNS myelination, in particular elucidating Myrf, myelin-gene regulatory factor, as a master controller transcription factor which is uniquely expressed by oligodendrocytes and is required for oligodendrocyte differention and myelination in vitro and in vivo. They have also made important steps forward in understanding the blood-brain barrier, showing that astrocytes are not required for its formation as long thought but showing that Wnt signaling and pericytes are both critical for its formation.

 
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