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 development and plasticity of synapses - the points of communication between neurons - during both healthy development and disease.

We focus on the role of neural-immune interactions in the patterning of neural circuits. We 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. C1q and downstream complement proteins target synapses for elimination by microglia - the resident phagocytes and immune cells of the brain. Our ongoing studies are directed toward defining the cellular and molecular mechanisms underlying microglia-synapse communication in the healthy brain. Using the visual system as our primary model system, we employ a combination of live imaging, molecular, biochemical and neuroanatomical approaches.

Although synapse elimination is largely considered a developmental process, early synapse loss and dysfunction are becoming increasingly recognized as a hallmark of many CNS neurodegenerative diseases. We hypothesize that synapse loss in CNS neurodegenerative diseases, such as Alzheimer's Disease, is caused by a reactivation, in the mature brain, of similar developmental mechanisms of synapse elimination. In addition, we are investigating the potential link between microglia, immune proteins and synapse loss in the pathogenesis of epilepsy and neurodevelopmental disorders, such as autism.