Role of Transient Receptor Potential Channel TRPM7 for Neural Circuit Function

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

Very often, experimentally induced mutation of a gene does not lead to a detectable physiological deficit because remaining components of the system are able to compensate for the loss of function. Occasionally, experimental mutation leads to a dramatic deficit, thereby providing insight into fundamental organizational principles. Mutation of the TRMP-7 gene results in a loss of motility in zebrafish. This loss appears to be due to a deficit in the ability of sensory neurons to respond to touch stimuli. The TRMP-7 gene encodes a protein that forms part of an ion channel whose failure to operate results in a dramatic behavioral phenotype. This project will focus upon understanding how this channel works to ensure proper development and operation of motor circuits by combining molecular biological and electrophysiological techniques. Specific aims include identification of neurons that have the TRMP7 protein, analysis of differences in neural circuitry between normal and mutant zebrafish, and functional analysis of different domains of the TRMP-7 gene. Studying the mechanisms underlying the dramatic behavioral changes caused by mutation of this single gene in the relatively simple nervous system of the zebrafish will very likely provide insight into fundamental genetic and neuronal mechanism found throughout the animal kingdom. An integral part of the project will be the involvement and training of undergraduates including those from under-represented groups, that will be recruited from the PI's courses and from the Summer Research Opportunity Program at the University of Michigan that is open to all American students. These students will work directly with the PI and be exposed to genetics, molecular biology, genomic databases, and electrophysiology. The goal will be to spark an interest in research and encourage students to pursue a Ph.D. program. Additionally, a new undergraduate course, 'Genes, Brain and Behavior', will be developed that will incorporate the methods and research findings from zebrafish mutants. This course will stress the genetic analysis of brain and behavior with particular attention to genetic model systems such as Drosophila, C. elegans, and zebrafish in addition to rodents. The course will incorporate the findings from analyses of zebrafish behavioral mutations including those derived from the PI's lab.