Gary L. Dunbar - US grants

Undergraduate students in two research methods courses are being provided with a computer lab to give them direct exposure to research methods. The computer lab is used by research design students to simulate experiments that illustrate fundamental design principles. The lab is used by research applications students to perform replications of some important recent experiments in a number of fields of psychology, and to select individual final experiments from a large number of studies already in the literature or to create variations of those studies. The equipment consists of a network of 12 stations and a controller/file server as well as additional hardware and software to conduct and simulate the experiments. Undergraduates can gain hands-on experience with some of the most important psychological experiments while learning the principles of research and research design. This should help them learn problem solving and probabilistic reasoning as well. Students should learn more and be more enthusiastic about research as a result of using this lab. The university will contribute an amount equal to the award.

This project is improving the psychology curriculum by implementing a basic level laboratory course in behavioral neuroscience. The course is providing undergraduates with hands-on experience using current techniques and instrumentation within the context of addressing a relevant research topic. Laboratory exercises are being integrated into a group experiment designed to address a specific research question of current interest. Each student is being given a rat to use for learning a sequence of basic techniques: lesioning, behavioral assessment (using computerized technology), histological procedures, and quantification of their neuroanatomical samples (using a computerized image analysis system). Data from all students is being pooled and analyzed individually (using SAS software). Each student is then writing up the results within the context of the research question that the group experiment addressed. Students are thus being better prepared for further inquiry in the neurosciences through advanced courses in the curriculum.

DESCRIPTION (Adapted from applicant's abstract): The proposed research is designed to develop an effective treatment for Huntington's disease. The study will test the potential of GM1 gangliosides as a treatment for both the short and long-term behavioral and anatomical effects caused by intrastriatal administration of quinolinic acid, an animal model of Huntington's disease. The specific aims will be to test whether or not pretreatment of GM1 can attenuate quinolinic acid-induced, 1) spatial learning deficits, 2) episodic barrel rolling behavior and tonic-clonic forepaw movements, 3) hyperactivity, 4) weight loss, 5) striatal atrophy, 6) ventricular dilatation, 7) gliosis, 8) neuronal death and 9) specific loss of GABA containing neurons. Two groups of rats will be given bilateral intrastriatal injections of quinolinic acid while a third group will receive injections of vehicle. Daily intraperitoneal treatments of either GM1 gangliosides or saline will be started three days prior to surgery and continued through post-operative day 14. Barrel rolling and tonic-clonic forepaw movements will be recorded during the six hours following surgery. Morris water maze testing will be conducted during post-operative days 6 to 14 for half the rats in each group, and post-operative days 62 to 70 for the other half of each group. Nocturnal locomotor activity will be assessed for a 12 hour period the day before surgery and on post-operative days five for all rats, on post-operative day fourteen for half the rats in each group and post-operative day 70 for the other half of each group. Following testing, the brain will be cut in ten micron sections and processed using cresyl violet and GABA immunocytochemistry. Area measures for gliosis, ventricular dilation and striatal atrophy, along with cell counts in the striatum, will be conducted in order to evaluate whether or not GM1 can protect against quinolinic acid-induced neuronal death and other anatomical alterations. Collectively, the behavioral and neuroanatomical results are intended to provide valuable information concerning the potential of GM1 as treatment for Huntington's disease.

An award is made to Central Michigan University to purchase a fluorescence-activated cell sorter (FACS). A FACS instrument measures multiple physical characteristics of single cells as they flow in a fluid stream one cell at a time past a point of measurement. Thousands of cells per second are passed through one or more laser beams and the light that is emitted or scattered from the cell is detected. The system converts the detected light signals into electronic signals that are processed by a computer software program. Cell properties that can be measured include number, size, shape, and fluorescence intensity. A FACS can also sort cells into different populations based on these properties. The acquisition of a FACS will make a substantial improvement in the ability of faculty at CMU to conduct leading-edge research. The FACS will be used by at least 21 faculty from the Biology, Chemistry, and Psychology Departments and the College of Medicine. The faculty users will use the FACS in many diverse research projects ranging from assessing the microbial diversity of the Great Lakes to producing stem cells for transplantation into brains of animals.

The acquisition of the FACS will also direct the training of the next generation of scientists by providing access to state-of-the-art equipment. It is estimated that 35 students/year will be trained to use the FACS through faculty-directed research projects. In addition, several of the faculty users serve as research mentors for undergraduate students participating in programs that are designed to increase the diversity of students pursuing careers in biological research. Many more students will be exposed to the FACS through coursework. The PI and co-PIs will develop a short course on FACS technologies available to faculty and students interested in utilizing the instrument for research. In addition, there are several current 500-level Biology and Neuroscience courses servicing both undergraduates and graduate students in which laboratory exercises using flow cytometry and cell sorting will be incorporated. The FACS will potentially benefit society through research projects that assess and protect the environmental health of the Great Lakes, further our knowledge of basic cellular processes, and understand brain function.