Projects

Current Projects | Archived Projects
There are 5 current projects in the NDRC.

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Synapses, Glia, and NRG1 signaling in schizophrenia

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Principal Investigator(s)
John Gilmore

Funding Agency
NIMH

Project Duration
12/01/2005 to 11/30/2010

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The purpose of this project is to model gene-environment interactions that contribute to abnormal brain development and risk for schizophrenia and other neurodevelopmental disorders. Exposure to infection causes a neuroinflammatory response that includes persistent activation of microglia and astrocytes. Given the increasing evidence that glia play a major role in synapse formation and stabilization, we hypothesize that exposure to infection causes abnormal synapse development through this activation of glia. We further hypothesize that glia activation regulates NRG1-erbB4 signaling at the synapse, providing a molecular basis for a gene-environment interaction that inhibits synaptogenesis in the developing cortex and increases risk for schizophrenia.


The proposed translational research will use an animal model of prenatal exposure to infection to study the effect of glial activation on synapse development and NRG1-erbB4 signaling in the neonatal cortex. Recent studies in mature animals indicate that infection can also inhibit neurogenesis, therefore we will study whether exposure to maternal infection can inhibit neurogenesis in the prenatal cortex. To study gene-environment interactions, we will assess synapse development and behavioral phenotypes in NRG1 and erbB4 knockout mice after exposure to prenatal infection. Finally, we will translate this work to human brain by studying the development of synapses, glia, NRG1 and erbB4 in the prefrontal cortex of humans, aged 0 to 25 years.