Mapping and Restoring Synaptic Connectivity in Brain Disorders

2016 Scientific Innovations Award
Thomas Biederer, Ph.D.
Department of Neuroscience
Tufts University

Dr. Biederer’s work focuses on how nerve cells in the brain communicate with each other through cellular connections called synapses. Synapses are formed and remodeled in the maturing and adult brain to rewire circuits. Synaptic aberrations are linked to autism spectrum disorders and schizophrenia. This proposal aims to map the underlying disease-linked synaptic changes and investigate novel interventions. Our approach will be based on animal models of autism spectrum disorders and schizophrenia, using genetically modified mice that harbor mutations in genes that cause these disorders in humans. These mouse models replicate core features of these brain diseases. First, we will develop methods to visualize for the first time the synaptic connections that are used during cognitive processes. We will employ this method to map connectivity changes in models of autism and schizophrenia. Second, we will introduce specific genes to intervene in the mature brain and increase the formation of connections. We will test whether this intervention helps the brain to re-wire itself and improves behavioral functions in autism spectrum disorders and schizophrenia. We expect this research to help us better understand synaptic wiring during cognition and to determine how we can use the body’s own ability to organize connectivity to restore deficits in brain disorders.

Other Awards

Chaolin Zhang, Ph.D., Columbia University
Human-specific Alternative Splicing, Brain
Development, and Ciliopathies
Like movie frames needing to be edited to tell an engaging story, pieces of genetic information stored in DNA for each gene need to be sliced and rejoined, through a…
Jason Shepherd, Ph.D. University of Utah
Virus-like Intercellular Signaling Underlying Autoimmune Neurological Disorders
Dr. Shepherd’s lab discovered that a brain gene critical for memory and cognition, Arc, has biochemical properties like retroviruses such as HIV. Arc protein can form virus-like protein capsids that…
Yuki Oka, Ph.D., California Institute of Technology
Molecular Mechanisms of Osmolality Sensing in the Mammalian Brain
Animals constantly detect and process sensory signals to react appropriately. External sensory information (e.g., light and sound) serves as prominent environmental cues to guide behavior. On the other hand, our…
Angelique Bordey, Ph.D., Yale University
The Role of Ribosomes in Synaptic Circuit Formation and Socio-Communicative Deficits
Dr. Bordey and her lab’s proposal aims at identifying a molecular mechanism responsible for autism-like socio-communicative defects in the developmental disorder, tuberous sclerosis complex (TSC). TSC is a genetic disorder…