Synapses,Channels, And Transduction In Neuroscience
Kenneth J Muller, Professor
Physiology And Biophysicsuniversity Of Miami School Of Medicine
Grant 5T32NS007044-34 from National Institute Of Neurological Disorders And Stroke IRG: NST
Project start date: 1975-07-01
Project end date: 2011-06-30
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Synapses,Channels, And Transduction In Neuroscience
Kenneth J Muller, Professor
Physiology And Biophysicsuniversity Of Miami School Of Medicine
1507 Levante Avenue
coral Gables, Fl 33124
Grant 5T32NS007044-33 from National Institute Of Neurological Disorders And Stroke IRG: NST
Abstract: This is a renewal application for a long-standing, highly focused training program that provides predoctoral and postdoctoral trainees with intensive research experience in the areas of synapses, ion channels, and transduction, while ensuring that the trainees have a thorough grounding in the basic neurosciences. The approaches involve the use of advanced molecular biological, physical, chemical, electrical, mathematical, and computational techniques to study fundamental questions in these focused areas of cellular and molecular neuroscience in which the 20 training faculty have expertise. Predoctoral trainees will enter the program after taking an interdisciplinary group of graduate courses and specialized courses tailored to their needs and interests. Under a mentor´s direction they will do original research culminating in a Ph.D. degree. Postdoctoral trainees are offered a choice of research projects from which they develop their own independent research. All trainees receive much individual attention from program and allied faculty. Training involves a broad variety of research activities including presentations and participation in seminars and journal clubs with a large and closely interacting group of neuroscientists. The trainees also take part in career and ethics workshops and gain some teaching experience. The aim of this training program is to produce scientists of high quality, capable of working at the forefront of their research area, broadly knowledgeable in the basic neurosciences, and able to communicate effectively. The trainees will be qualified for diverse advanced positions in the biomedical sciences, ranging from the traditional academic to those in private industry and government. In keeping with the rigorous nature of the program, we seek first- rate applicants. Predoctoral candidates must be strong academically, with demonstrated interest in, and aptitude for, scientific inquiry. Postdoctoral candidates with Ph.D.s must have completed a high quality research project in a relevant discipline; individuals with M.D. degrees are actively recruited. Support is requested for 2 pre- and 2 postdoctoral trainees and short-term training for 4 medical students. The focused training forms the basis for understanding many diseases and disorders of the nervous system, including neurodegeneration, channelopathies, and dysfunction from genetic mutation. By training neuroscientists for research in these critical areas, the program is expected to contribute substantially to public health
Project start date: 1975-07-01
Project end date: 2011-06-30
5T32NS007044-33 (2008): $218558
5T32NS007044-32 (2007): $317942
Grants awarded to Kenneth J Muller
Loss And Restoration Of Function After Neuronal Injury
Kenneth J Muller, Professor
University Of Miami School Of Medicine 1507 Levante Avenue Coral Gables, Fl 33124
Grant 5R01NS034927-12 from National Institute Of Neurological Disorders And Stroke IRG: IFCN
Abstract: A major problem of neuroscience is to understand mechanisms for behavioral recovery following neural injury. Our collaborative work supported by this grant has provided the first demonstration that capacity for non-associative learning is restored by regeneration of neuronal connections, that a specific connection is crucial for sensitization, although return of function does not immediately follow reconnection, and it suggests new mechanisms for non-associative learning. It is the basis for the proposed cellular and behavioral studies on loss and recovery of the capacity for sensitization following damage to central circuits. Recent work indicates that vertebrates and invertebrates share fundamental mechanisms for axon growth and guidance in addition to neuronal function. In leeches we combine in-depth work on modulation of defensive shortening from one laboratory and work on synapse regeneration by sensory neurons and interneurons including the S-cell from the other. Thus we have shown that the capacity for sensitization of reflexive shortening requires the S-cell, which is restored by regeneration of one of the S-cell s synapses, but with a delay. Proposed experiments will give key information about cellular changes that underlie learning as related to mechanisms for nervous system recovery from injury. Advantages of leeches for such studies include (1) their identifiable neurons, able to re-establish specific connections, (2) selective laser-cutting of single axons in living animals, and (3) stable recordings from identified neurons in behaving animals. Experiments will determine (1) mechanisms for axotomy-induced loss of capacity for sensitization, (2) mechanisms that restore the full capacity for sensitization after injured S-cells reconnect, and (3) the relationship between regulation of functional geometry and repair of intersegmental sensory projections. Methods will include electrophysiology, injection of intracellular markers, laser microbeam axotomy, behavioral testing of leeches including semi-intact preparations, histochemistry, immunocytochemistry, immunoblotting, and confocal and electron microscopy. The studies will reveal basic mechanisms for restoration of plastic properties of the nervous system after injury while at the same time provide insights into the cellular circuitry for non-associative learning.
Keywords: behavioral habituation /sensitization, functional ability, interneuron, nerve injury, nervous system regeneration, neural plasticity, afferent nerve, axon reaction, electrophysiology, neural conduction, Hirudinea, behavior test, behavioral /social science research tag, confocal scanning microscopy, electron microscopy, immunocytochemistry
Project start date: 1995-06-01
Project end date: 2009-04-30
5R01NS034927-12 (2007): $310648