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SPIE Professional July 2015

Neurophotonics honors Larry Cohen

The April-June issue of the SPIE journal Neurophotonics features a tribute to the brilliance and originality of Lawrence B. (Larry) Cohen as well as reports on the latest advances in voltage-sensitive dyes and multiple-site optical recording methods enabled by the work of Cohen and his team. Journal editors say Cohen’s research has paved the way for advances in functional imaging of the electrical activity of live tissue in real time.

In an editorial in the special section, guest editors Brian Salzberg of the University of Pennsylvania (USA) and Dejan Zecevic of Yale University School of Medicine (USA), where Cohen has been a professor for 35 years, laud Cohen’s dominant role in developing and applying optical methods in cell physiology, biophysics, and neuroscience.

From left, Amiram Grinvald, Larry Cohen, Kohtaro Kamino, Brian Salzberg, and William Ross at a gathering in Tokyo in 2000.
Photo courtesy Kohtaro Kamino.

Advances in functional imaging of the nervous system and other physiological systems — barely conceivable without optical mapping using potentiometric probes and, more recently, genetically encoded voltage-sensitive proteins pioneered by Cohen and his colleagues — are only the beginning, Salzberg and Zecevic noted.

The era in which optical methods, especially fluorescence, but also absorbance, birefringence, and light scattering, are applied to an extremely large range of biological preparations could not have occurred without Cohen’s pioneering and extremely fruitful work, they said.

More than a dozen papers demonstrate the legacy of Cohen’s research, beginning in the late 1960s.

John Nicholls of the International School for Advanced Studies (Italy) writes that at that time, Cohen devoted himself to two key problems: finding the dyes that would best light up during activity and developing the best methods for recording optical signals.

“He moved up from single axons, to groups of nerve cells in invertebrates, and then to an important biological problem: the organization of olfactory processing that gives rise to the sense of smell,” Nicholls says. “This progression took many years, but Larry never swerved from his aim: to observe how tens, or hundreds, or thousands of nerve cells process information in real time.”

Kohtaro Kamino of Tokyo Medical and Dental University worked in Cohen’s lab at Yale and witnessed the birth of this frontier field. In the 1970s, when large photodiode arrays were not yet available, Cohen, together with Salzberg and then Amiram Grinvald, used individual light guide modules to introduce multiple-site optical recording methods into neurobiology.

With colleagues including Kamino, Cohen began using 5x5-element photodiode arrays, and by the early 1990s had built systems incorporating 464-element arrays. Kamino’s article in the special section details how this early work influenced his research centering on capturing development of cardiac and neural systems in early-stage chick and rat embryos.

Among other articles in the special section, “Linker length and fusion site composition improve the optical signal of genetically encoded fluorescent voltage sensors,” by Arong Jung of the Korea Institute of Science and Technology (KIST) et al., describes how the linker-length sequence affects the optical signal of the fast fluorescent probes first developed in Cohen’s lab. Cohen later went on to be a senior researcher at KIST.

Another article, “Branch specific and spike-order specific action potential invasion in basal, oblique, and apical dendrites of cortical pyramidal neurons,” coauthored by Wen-Liang Zhou of the University of Connecticut Stem Cell Institute, uses the principles of optical imaging developed by Cohen to investigate action potential invasion into thin dendritic branches of prefrontal cortical L5 pyramidal neurons.

These and all other articles in the Neurophotonics are freely available on the SPIE Digital Library through the end of 2015.

DOI: 10.1117/2.4201507.17

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