RESEARCH INTEREST

Optical measurement of membrane potential in a variety of excitable tissues including vertebrate nerve terminals, neurons in culture, and the enteric nervous system; light scattering changes related to secretion from nerve terminals.


RESEARCH TECHNIQUES

Optical measurement of membrane potential; quantitative fluorescence measurement; quantitative absorbance measurement; tissue culture of identified invertebrate neurons; light scattering and optical heterodyning; voltage clamp.


RESEARCH SUMMARY

Certain substances, when bound to the membranes of neurons, cardiac and skeletal muscle, salivary acini, and other cells, behave as molecular indicators of membrane potential. The optical properties of these molecules, most notably fluorescence and absorbance, vary in a linear fashion with potential and may, therefore, be used to monitor action potentials, synaptic potentials, or other changes in membrane voltage from a large number of sites at once, without the necessity of using electrodes. Our laboratory is engaged in the development of more sensitive probes, extending the technology associated with their use, and in using these molecular voltmeters for optical recording of membrane potential from hitherto inaccessible regions of single neurons such as axon and neuroendocrine terminals and axonal and dendritic processes, and from many sites simultaneously, with single cell resolution, in simple mammalian nervous systems, in order to study the spatial and temporal patterning of activity.

Also, we are continuing to exploit the optical properties of potentiometric probes to detect the voltage changes in the nerve terminals of vertebrates, and to correlate alterations in the shape of the nerve terminal action potential with the release of neuropeptides monitored through rapid changes in light scattering.


KEY REFERENCES

Kim, G.H., P. Kosterin, A.L. Obaid, and B.M. Salzberg. A mechanical spike accompanies the action potential in mammalian nerve terminals Biophysical Journal. 92:3122-3129, 2007. Online PDF File   Related Online PDF File

Salama, G., Choi, B.R., Azour, G., Lavasani, M., Tumbev, V., Salzberg, B.M., Patrick, M.J., Ernst, L.A., Waggoner, A.S. Properties of new, long-wavelength, voltage-sensitive dyes in the heart, J Membr Biol 208(2):125-140, 2005.

Kosterin, P., Kim, G.H., Muschol, M., Obaid, A.L., Salzberg, B.M. Changes in FAD and NADH fluorescence in neurosecretory terminals are triggered by calcium entry and by ADP production. J Membr Biol. 208(2):113-124, 2005.

Salzberg, B. Optical recording of electrical activity, J Membr Biol. 208(2):89-90, 2005.

Fisher, J.A., Salzberg, B.M., Yodh, A.G. Near infrared two-photon excitation cross-sections of voltage-sensitive dyes. J Neurosci Methods, 148(1):94-102, 2005.

Obaid, A.L., Nelson, M.E., Lindstrom, J., and Salzberg, B.M.,Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous sytem, J Experi Biol 208:2981-3001, 2005.

Salzberg, B.M., Kosterin, P.V., Muschol, M., Obaid, A.L., Rumyantsev, S.L., Bilenko, Yu., and Shur, M.S. An ultra-stable non-coherent light source for optical measurements in neuroscience and cell physiology, J. Neuroscience Methods 141(1):165-169 2005.

Obaid, A.L., L.M. Loew, J.P. Wuskell, and B.M. Salzberg. Novel naphthylstyryl-pyridinium potentiometric dyes offer advantages for neural netowrk analysis. J. Neuroscience Methods 134:179-190, 2004. Online PDF File

A.L. Obaid, T. Koyano, J. Lindstrom, T. Sakai, and B.M. Salzberg. Spatio-temporal Patterns of Activity in an Intact Mammalian Network with Single Cell Resolution: Optical Studies of Nicotinic Activity in an Enteric Plexus. J. Neuroscience 19:3073-3093, 1999.

Obaid, A.L. and Salzberg, B.M. Micromolar 4-aminopyridine enhances invasion of a vertebrate neurosecretory terminal arborization: optical recording of action potential propagation using an ultrafast photodiode-mosfet camera and a photodiode array. J. Gen. Physiol. 107:353-368, 1996.

Rohr, S. and Salzberg, B.M. Characterization of impulse propagation at the microscopic level across geometrically defined expansions of excitable tissue: multiple site optical recording of transmembrane voltage in patterned growth heart cell cultures. J. Gen. Physiol. 104:287-309, 1994.

Parsons, T.D., Salzberg, B.M., Obaid, A.L., Raccuia-Behling, F. and Kleinfeld, D. Long-term optical recording of patterns of electrical activity in ensembles of cultured aplysia neurons. J. Neurophysiol. 66:316-333, July 1991.