Interferometric measurement of nerve signaling

Current Work
We are developing novel interferometers for measuring intrinsic mechanical and optical signals which accompany electrical activity in nervous tissues. Intrinsic changes include swelling [1], refractive index changes [2,3], and hemodynamic changes [4] in whole brain. The potential advantages of intrinsic imaging over electrophysiological methods include the ability to perform long-term noninvasive studies, the ability to record from very small diameter processes (axon/dendrites) for which electrophysiology is impossible, and scalability of the technique to recording from large numbers of neurons simultaneously.

Using a novel dual-beam heterodyne low coherence interferometer, we have performed single-shot, non-contact measurements of the ~5 nm surface displacements which accompany the compound action potential in an excised lobster nerve [5]. We have integrated the interferometer with an inverted microscope and are investigating related mechanical motions in cultured rat hippocampal neurons. Scanning the sample or interferometer beam also allows imaging of cellular motions on the sub-nanometer scale. A related interferometric technique was used to measure cell volume changes in a cell monolayer [6].

Recent Publications

1. K. Iwasa, I. Tasaki, R. C. Gibbons, “Swelling of nerve fibers associated with action potentials,” Science 210: 338-339, (1980).
2. R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher and D. Kleinfeld, “Noninvasive Detection of Changes in Membrane Potential in Cultured Neurons by Light Scattering”, Proc. Natl. Acad. Sci. 88(21): 9382 (1991).
3. D. Kleinfeld and A. LaPorta, “Detection of action potentials in vitro by changes in refractive index,” in Light Scattering Imaging of Neural Tissue Function, D. M. Rector and J. S. George eds. (Humana Press, Totowa, New Jersey, 2003).
4. A. Grinvald, E. Lieke, R. D. Frostig. C. D. Gilbert, T. B. Wiesel, “Functional architecture of cortex revealed by optical imaging of intrinsic signals”, Nature 324: 361-364 (1986).
5. C. Fang-Yen, M. Chu, H. S. Seung, R. R. Dasari, and M. S. Feld, “ Non-contact measurement of nerve displacement during action potential with a dual-beam low coherence interferometer”, Optics Letters, (2004).
6. C. Yang, A. Wax, M. S. Hahn, K. Badizadegan, R. R. Dasari, and M. S. Feld, “A phase-referenced interferometer with sub-wavelength and sub-Hertz sensitivity applied to the study of cell membrane dynamics,” Optics Letters 26: 1271-1273 (2001).