Genomes and Genes




Principal Investigator: JAMES WILLOTT
Abstract: The overall goal is to develop, evaluate, and standardize a set of procedures that use acoustic startle response (ASR) modification to identify phenotypes for use in research on hearing impairments, certain neurobehavioral disorders, learning ability, and emotionality. Specific aims are to develop procedures and establish performance "norms" using common strains of mice. Basic properties of the ASR will be determined. Prepulse inhibition (PPI) will be used to identify possible hearing deficits. PPI is also a measure of "sensory gating," and is diminished in human patients with neurobehavioral disorders such as schizophrenia. If a mouse exhibits poor PPI but has good hearing (determined by a second-level screening test using the auditory brainstem response), the poor PPI would be taken as evidence for a deficit in sensory gating. PPI will be further evaluated as well, increasing the likelihood of detecting gating deficits. Habituation of the ASR will be assessed also, because this is abnormal in schizophrenia and anxiety disorders. The fear-potentiated startle (FPS) and freezing paradigms will be used to assess learning ability and emotionality. Both can be evaluated in the same screening protocol. Poor performance on either task would suggest an emotional learning deficit. Stimulus and testing paradigms will be refined and optimized in conjunction with the testing of the common strains of mice. Performance means and variances will be established for each strain, providing criteria for testing of existing mutants. The startle and PPI paradigms will be developed by Dr. Willott at Northern Illinois University; the FPS and freezing by Dr. Falls at the University of Vermont. Ultimately, the methods will be integrated, refined, and tested on existing neurological and other mutant mice at the Jackson Laboratory under the supervision of Dr. Johnson. This will be accompanied by development of an easy-to-use software/ hardware package that will integrate all screening techniques in a single, serial protocol for use on individual mice.
Funding Period: 2000-01-01 - 2003-12-31
more information: NIH RePORT