Research

Overview

Growing evidence from epidemiology, genetics and clinical neuroscience implicates neuroimmune mechanisms in the pathophysiology of schizophrenia (SZ) and other developmental psychiatric disorders. A new class of animal models of maternal immune activation (MIA), expressing developmentally phenotypic features related to SZ, has been developed; however, little is known about the mechanisms by which MIA results in changes to brain development, connectivity and behavior. The UC Davis Conte Center seeks to bridge that gap. Our interdisciplinary team of neuroscientists has worked together to develop hypotheses, design experiments and collect preliminary data to develop a unique set of closely integrated projects. The Center comprises an accomplished group of investigators from molecular and cell biology, systems and behavioral neuroscience, biomedical engineering, neuroimaging, and clinical neuroscience and a highly integrated set of studies conducted across species and scale to test the hypothesis that one important origin of schizophrenia is a dysregulation of immune molecules that play a key role in the normal development and functioning of connections in the brain. These changes are hypothesized to lead to altered structural and functional connectivity and eventually to the disturbances of cognition, perception and emotion that characterize schizophrenia. Across the Center projects, synaptic changes, gene expression, structural and functional connectivity, neural inflammation and behavior will be measured in unique animal models at multiple ages to determine the timing and hierarchy of the effects of MIA. When possible, parallel studies in humans will be conducted to establish the clinical relevance of the MIA animal models.

The Center will pursue two Specific Aims to determine:

  1. whether MIA increases risk for neurodevelopmental psychiatric disorders in offspring by altering neural circuitry through dysregulated signaling of immune molecules and gene networks throughout development;
  2. the timing of the appearance and progression of structural and functional changes in the brains of MIA offspring relative to the onset of dopamine dysregulation, neural inflammation, and SZ-related behavioral disturbances in the MIA models and compare these data to those seen in first-episode SZ using novel MRI based brain imaging approaches.

The projects will measure changes in synaptic connectivity, gene expression, structural and functional connectivity, neural inflammation, and behavior in two unique MIA models at multiple ages to determine the relative timing and hierarchy of these changes and understand the underlying mechanisms. These studies in the animal models will be complemented by novel analyses of synaptic connectivity and gene expression in post mortem human tissue from SZ.

The UC Davis Conte Center comprises four distinct research Projects, an enabling Research Core, and an Administrative Core.