From: LARRY KLAES (ljk4_at_msn.com)
Date: Sat Feb 14 2004 - 08:01:20 PST
>From: cunews_at_cornell.edu
>Reply-To: cunews_at_cornell.edu
>To: CUNEWS-LIFE_SCIENCE-L_at_cornell.edu, CUNEWS-SCIENCE-L_at_cornell.edu
>Subject: Cornell News: recording nerve cell signals
>Date: Fri, 13 Feb 2004 18:48:58 -0500
>
>New optical recording technique can see millisecond nerve impulses in
>healthy and diseased brains, Cornell biophysicists report
>
>FOR RELEASE: Feb. 13, 2004
>
>Contact: Roger Segelken
>Office: 607-255-9736
>E-mail: hrs2_at_cornell.edu
>
>
>ITHACA, N.Y. -- Combining the bright laser light of multiphoton microscopy
>with specially developed dyes and a phenomenon called second-harmonic
>generation, biophysicists at Cornell University and Université de
>Rennes, France, have made high-resolution images of
>millisecond-by-millisecond signaling through nerve cells.
>
>The first demonstration of the new technique, reported as the cover story
>in the Jan. 28, 2004, issue of The Journal of Neuroscience, was in neurons
>of the lowly sea slug, Aplysia. But the Cornell researchers anticipate that
>eventually the technique will be used in brain tissues of higher animals
>and could help decipher the wiring of the brain and possibly explain
>consequences of degenerative brain diseases such as Alzheimer's.
>
>"This technique gives us the ability to look at membrane potential in
>nerve-cell signaling with high resolution deep in intact tissue, where
>previous methods were not applicable," says Daniel A. Dombeck, lead author
>on the journal paper and a graduate student in the Developmental Resource
>for Biophysical Imaging Opto-Electronics laboratory of Watt W. Webb,
>professor of applied physics at Cornell.
>
> "With submillisecond resolution, we're beginning to see how much the
>electrical signals can vary between different places of a single neuron,"
>says Dombeck. "With further development, we should be able to see how
>pathology affects electrical signals. We'd like to know, for example, how
>much Alzheimer's plaques affect the signal transmission in axons."
>
>Multiphoton microscopy, including second-harmonic generation, produces
>high-resolution, three-dimensional pictures of tissue with minimal damage
>to living cells, using a laser that produces a stream of extremely short,
>intense pulses. When two or three photons strike a biological molecule at
>the same time, their energies combine. This has the cumulative effect of
>delivering one photon -- with nearly twice the energy -- to the sample. By
>adjusting the plane of focus, a multiphoton microscope can produce a vivid
>image deep within living tissue. And by "stacking" multiple images at
>various depths of focus, the system produces three-dimensional images or
>movies.
>
>Each action potential is a single nerve impulse, traveling through a neuron
>as chemically gated ion channels open and close with changes in electrical
>polarity. The quantum physical optics phenomenon, second-harmonic
>generation (SHG) is the first multiphoton technique capable of detecting
>action potentials. SHG is particularly useful for imaging these impulses
>because it picks out only the cell membrane where impulses occur and does
>not suffer from other background signals. This selectivity, combined with
>SHG's fast response to the electrical signals, allows for high
>signal-to-noise ratio recordings of neuron signaling.
>
>SHG in light waves, Dombeck explains, is similar to the more familiar
>phenomenon in sound waves, such as those produced in the body of a guitar.
>The second-harmonic of a guitar string's vibration is twice as high in
>pitch when it resonates in the wood body of the guitar. Similarly, laser
>light striking molecules of uniform polarity produces a second-harmonic
>wave of twice the energy -- or half the wavelength -- which is easily
>detected by the microscope in the forward propagating direction.
>
>Thus, every change in polarity and every action potential is optically
>imaged in submicrometer and millisecond spatiotemporal resolution. Previous
>attempts in other laboratories to record fast electrical signals in live
>cells with SHG had achieved, at best, about 1-second resolution and were
>not detecting impulses a few milliseconds in duration.
>
>"Nevertheless, with all the advantages of second-harmonic generation, we
>still faced two obstacles in imaging action potentials in living tissue,"
>says Webb, the co-inventor (with Winfried Denk) of multiphoton microscopy.
>"First, many dyes are chemically toxic to neurons of living animals, and
>secondly, the intense laser pulses can cause phototoxic damage."
>
>These obstacles were overcome by using a less-toxic dye, a longer
>illumination wavelength and by limiting the duration and intensity of the
>laser pulses. "Also, we conducted the first demonstration of this technique
>in a single cell of a pretty robust creature, the sea slug. But to use this
>imaging technique in more sensitive animals, we need to find an even less
>toxic dye," says Webb, adding that this will be a challenge.
>
>But expanding the imaging from a single neuron to a larger network will be
>simple enough, says Dombeck. With the microscope's field of view, he says,
>it should be possible to record electrical signaling between many neurons
>at once.
>
>Development of the new technique was supported, in part, by the Defense
>Advanced Research Projects Agency, the National Institutes of Health and by
>Centre National de la Recherche Scientifique, the French national
>science-funding agency. The biophysicists have applied for a patent on the
>process, titled "Nonlinear Optical Detection of Fast Cellular Electrical
>Activity," through the Cornell Research Foundation.
>
>
>
> Related World Wide Web sites: The following sites provide additional
>information on this news release. Some might not be part of the Cornell
>University community, and Cornell has no control over their content or
>availability.
>
> Biophysical imaging at Cornell: <http://www.drbio.cornell.edu/>
>
>-30-
>
>
>
>The web version of this release, with accompanying photos, may be found at
>http://www.news.cornell.edu/releases/Feb04/Optical_recording.hrs.html
>--
>
>Cornell University News Service
>Surge 3
>Cornell University
>Ithaca, NY 14853
>607-255-4206
>cunews_at_cornell.edu
>http://www.news.cornell.edu
>
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