Regulation of Dopamine Release in the Hyperactive Mouse Mutant Coloboma

Grant Type
Basic
Grant Year
1997
Institution Location
PA
Institution Organization Name
Penn State University
Investigators Name
Hess, Ellen, PhD

Pathologic hyperactivity is observed in several neurologic disorders including Tourette Syndrome (TS). We have identified a mutant mouse called coloboma that exhibits extreme hyperactivity. Our goal is to identify abnormalities in the function of neurons within the brains of these mice that cause this hyperactivity thereby providing a biological framework for a better understanding of the causes of hyperactivity in humans. The hyperactivity exhibited by coloboma mice is caused by a mutation in the Snap gene which encodes a protein known to be involved in neurotransmitter release. (Neurons communicate with each other by liberating or releasing small molecules called neuro¬transmitters which act as chemical signals.) Defects in neurotransmit¬ter release cause the hyperactivity in these mutant mice. Thus mouse mutant coloboma provides an exciting and unique opportunity to examine genetic and cellular abnormalities in neurotransmitter release related to the expression of hyperactivity. We will examine the abnormalities in neurotransmitter signalling that cause the hyperactivity in these mutant mice. It is now possible to measure small packages of neurotransmitter released from a single cell using electrochemical techniques, a powerful tool for assessing chemical signaling. Extremely sensitive microelectrodes readily detect neurotransmitters such as dopamine. By placing these electrodes in close proximity to a neuron, packages of neurotransmit¬ter released in the hyperactive mouse mutants will be measured to determine how the mutation affects the amount of neurotransmitter released as well as just how often neurotransmitter release occurs. These experiments represent the first steps in understanding how a specific genetic defect ultimately produces hyperactivity. Results of these experiments will provide important insight into the role of neurotransmitter release in pathologic hyperactivity, and may poten¬tially produce more directed treatment strategies. Ellen J. Hess, Ph.D. The Milton S. Hershey Medical Center/ Penn State University College of Medicine, Hershey, PA Award: $33,000* * Subsequent to award approval by TSA’s Scientific Advisory Board, this investigation was funded by the NIH/NINDS. Tourette Association of America Inc. – Research Grant Award 1997