Physiology and Biophysics Faculty

Research Interests

Our laboratory studies synaptic transmission and mitochondrial function at vertebrate (lizard, mouse) motor nerve terminals. We use fluorescent indicator dyes and a confocal microscope system to study changes in cytosolic and mitochondrial [Ca2+], mitochondrial membrane potential and vesicular release in motor terminals stimulated with trains of action potentials. Quantal transmitter release is assayed by electrophysiological recording from the underlying muscle fiber. Our work has demonstrated that mitochondrial Ca2+ uptake is the major short-term mechanism by which motor nerve terminals handle the large Ca2+ loads they encounter during repetitive nerve stimulation. When mitochondrial Ca2+ uptake is inhibited, cytosolic [Ca2+] and asynchronous quantal release rise to much higher levels during stimulation, but phasic evoked release decreases rapidly and neuromuscular transmission fails.

Currently we are studying mechanisms by which motor terminal mitochondria extrude the Ca2+ they take up, how this Ca2+ extrusion influences transmitter release, and how motor terminal metabolism changes during and after nerve stimulation. We are also studying motor terminal function in the SOD1G93A mouse model of amyotrophic lateral sclerosis. There is evidence that the motoneuron death in this disease begins peripherally and involves mitochondrial dysfunction. We are testing several hypotheses concerning why motor terminals might be especially vulnerable in SOD1G93A mice.

Techniques: Measurement of stimulation-induced changes in [Ca2+] and metabolism in motor terminals using fluorescent indicators and a high-sensitivity confocal microscope system specially designed for studies of living mammalian tissue. Intracellular electrophysiological recording from muscle end-plates. Immunohistochemical staining of motor terminals and spinal cord ventral horn. Computer-assisted analysis of images and quantal release using specialized software.

• Google Scholar Citations
• PubMed Citations

Selected Publications

1. White MG, Luca LE, Nonner D, Saleh O, Hu B, Barrett EF, Barrett JN (2005) Cellular mechanisms of neuronal damage from hyperthermia. Progress in Brain Research: Neurobiology of Hyperthermia (In Press).
2. Nonner D, Panickar K, Barrett EF, Barrett JN (2004) Bone morphogenetic proteins and neurotrophins provide complementary protection of septal cholinergic function during phosphatase inhibitor-induced stress. J Neurochem. 91(1):77-87.  
3. David G, Talbot J, Barrett EF (2003) Quantitative estimate of mitochondrial [Ca2+] in stimulated motor nerve terminals. Cell Calcium. 33(3):197-206. 
4. Vila L, Barrett EF, Barrett JN. (2003) Stimulation-induced mitochondrial [Ca2+] elevations in mouse motor terminals: comparison of wild-type with SOD1-G93A. Journal of Physiology, 549:719-728.
5. Talbot JD, David G, Barrett EF (2003) Inhibition of mitochondrial Ca2+ uptake affects phasic release from motor terminals differently depending on external [Ca2+]. Journal of Neurophysiology, 90:491-502.
6. David G, Barrett EF (2003) Mitochondrial Ca2+ uptake prevents desynchronization of quantal release and minimizes depletion during repetitive stimulation of mouse motor nerve terminals. Journal of Physiology, 548:425-438.  
7. David G and Barrett EF (2000) Stimulation-evoked increases in cytosolic [Ca2+] in mouse motor nerve terminals are limited by mitochondrial uptake and are temperature-dependent. J Neurosci 20:7290-7296.

Curriculum Vitae

• 1966 B.S. Psychology summa cum laude, University of Washington, Seattle, WA
• 1972 PhD Physiology and Biophysics, Univesrity of Washington, Seattle, WA
• 1972-1973 Postdoctoral Fellowship, Physiology, University of Colorado
• 1972-1973 Postdoctoral Fellowship, Neurobiology, Harvard Medical School 1974 Assistant Professor, Dept. of Zoology, University of Iowa
• 1974-1978 Assistant Professor, Dept. of Physiology and Biophysics, University of Miami School of Medicine
• 1978-1990 Associate Professor, Dept. of Physiology and Biophysics, University of Miami School of Medicine
• 1990-present Professor, Dept. of Physiology and Biophysics, University of Miami School of Medicine
• 1986-1993 Javits Neuroscience Investigator Award
• 1993-present Journal of Physiology (London) Editorial Board
• 1980-1984 NIH Review Committees: Neurology A 1992-1996 NIH Review Committees: Neurological Disorders Program Project B