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

Angelique Bordey, Ph.D., Yale University
The Role of Ribosomes in Synaptic Circuit Formation and Socio-Communicative Deficits
Our 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 with a 30-60% incidence…
Adam E. Cohen, Ph.D., Harvard University
To spike or not to spike? Mapping dendritic computations in vivo.
The brain is made of neurons, and neurons convert synaptic inputs to spiking outputs. How does a neuron decide when to spike?
Gina Turrigiano, Ph.D., Brandeis University
Homeostatic Maintenance of Neocortical Excitation-inhibition Balance by Ciliary Neuropeptidergic Signaling
Brain circuit wiring is adjusted during adolescence to generate fully functional circuits, and this process depends on an interaction between genetics and experience. During this period of experience-dependent development, excitatory…
Gregory Scherrer, Ph.D., The University of North Carolina at Chapel Hill
Mechanisms of Affective States and Drug Discovery at the Intersection of Chronic Pain and Opioid Addiction
Pain is normally a sensation that we experience when our body is exposed to damaging stimuli, such as the noxious heat of an open flame. However, when chronic, pain becomes…