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Researcher | Research Overview

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We are interested in interactions between the two fundamental cell types of the nervous system, neurons and glia. My laboratory seeks to understand how neuron-glia communication facilitates the formation, elimination and plasticity of synapses—the points of communication between neurons—during both healthy development and disease.

We focus on the role of neuron-glia and neural-immune interactions in the patterning of neural circuits. We and our collaborators have identified an unexpected role for glia and components of the innate immune system in synaptic pruning. We find that astrocytes induce neuronal expression of complement C1q, the initiating protein of the classical complement cascade (which tags unwanted cells and debris for elimination in the immune system). C1q and downstream complement proteins target synapses and are required for synapse elimination in the developing visual system. Importantly, we find that C1q becomes aberrantly upregulated and is relocalized to synapses in the early stages of glaucoma, suggesting that a similar elimination mechanism may be in place during both healthy central-nervous-system (CNS) development and neurodegenerative diseases.

Our ongoing studies are directed toward defining the cellular and molecular mechanisms underlying synapse elimination during health and disease, with emphasis on the role of complement in this process. In addition to our interest in CNS neurodegenerative diseases, we are currently collaborating with other laboratories to further probe the potential link between complement proteins and synapse loss in the pathogenesis of epilepsy and neurodevelopmental disorders.

A microglial cell labeled with green fluorescent protein (GFP). The microglial processes are closely positioned and interacting with retinal ganglion cell inputs (red and turquoise) in the dorsal lateral geniculate nucleus of the thalamus. Image was acquired from a postnatal day 30 mouse.

 

One current goal is to understand how synapses in the CNS are selectively targeted for elimination. Why does one synapse get eliminated while a nearby synapse stays intact? Our recent findings suggest that microglia—the immune cells of the CNS—may play an important role in the elimination process.

We are also interested in identifying the activity-dependent and molecular cues that regulate expression of complement proteins in the developing and diseased brain, and in determining the specific synaptic sites at which these proteins act. How might glial-derived signals impact other developmental processes, such as synaptogenesis and the myelination of axons? We employ a combination of live imaging, molecular, biochemical and neuroanatomical approaches to address these and other mechanistic questions.

Researcher | Research Background

Beth Stevens received her PhD in Neuroscience in 2003 from the University of Maryland, College Park and completed her postdoctoral fellowship at the Stanford University School of Medicine in 2008. She is a recipient of the 2008 Smith Family Award for Excellence in Biomedical Research, a 2010 Dana Foundation Award (Brain and Immunoimaging) and a 2010 Ellison Medical Foundation New Scholar in Aging award.  Dr. Stevens received the Presidential Early Career Award for Scientists and Engineers in 2012.  In 2015, she was selected for a MacArthur Foundation Fellowship.

Researcher | Publications