Neurophotonics celebrates latest advances, legacy of pioneering research in voltage-sensitive dye imaging

Pioneering work in Larry Cohen's lab influenced numerous researchers, paving the way for advances in functional imaging of the electrical activity of live tissue in real time

10 April 2015
Larry Cohen

Larry Cohen as a young researcher,
displaying a model of a chemcial
compound used in his
ground-breaking research.

BELLINGHAM, Washington, USA -- The latest issue of the journal Neurophotonics features a tribute to the brilliance and originality of Lawrence (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. Their research has paved the way for advances in functional imaging of the electrical activity of live tissue in real time, say journal editors.

Neurophotonics is published by SPIE, the international society for optics and photonics. All articles in the journal are open access on the SPIE Digital Library through the end of 2015.

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 Prof. Cohen and his colleagues -- are only beginning, noted guest editors Brian Salzberg (University of Pennsylvania) and Dejan Zecevic (Yale University School of Medicine) in their editorial in the special section.

Indeed, the guest editors said, 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 Larry Cohen's pioneering and extremely fruitful work.

Beginning in the late 1960s, 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," wrote John Nicholls (International School for Advanced Studies, Italy) in the journal. "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. 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 (Tokyo Medical and Dental University) worked in Cohen's laboratory at Yale University 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 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 April-June issue demonstrating the legacy of Cohen's research, "Linker length and fusion site composition improve the optical signal of genetically encoded fluorescent voltage sensors," by Arong Jung (Korea Institute of Science and Technology) et al. describes how the linker length sequence affects the optical signal of the fast fluorescent probes first developed in the Cohen lab.

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

Other papers include:

  • "Imaging with organic indicators and high-speed charge-coupled device cameras in neurons: some applications where these classic techniques have advantages," William Ross (New York Medical College) et al.
  • "Computer-generated holography enhances voltage dye fluorescence discrimination in adjacent neuronal structures," Amanda Foust (Paris Descartes University) et al.
  • "Route to genetically targeted optical electrophysiology: development and applications of voltage-sensitive fluorescent proteins," Walther Akemann (Imperial College London) et al.
  • "Voltage-sensitive dye imaging during functional development of the embryonic nervous system: a brief review with special thanks to Professor Larry Cohen," Yoko Momose-Sato (Kanto Gakuin University) and Katsushige Sato (Komazawa Women's University Faculty of Human Health)
  • "Using simultaneous voltage and calcium imaging to study fast Ca2+ channels," by Nadia Jaafari, Elodie Marret, and Marco Canepari (Grenoble Institute of Neuroscience)
  • "Optical recording of calcium currents during impulse conduction in cardiac tissue" by Florian Jousset and Stephan Rohr (University of Bern)
  • "All-optical mapping of barrel cortex circuits based on simultaneous voltage-sensitive dye imaging and channelrhodopsin-mediated photostimulation," Shun Qiang Lo (National University of Singapore) et al.

David Boas of Massachusetts General Hospital, Harvard Medical School, is the journal's editor-in-chief.

Neurophotonics is published in print and digitally in the SPIE Digital Library, which contains nearly 400,000 articles from SPIE journals, proceedings, and books, with approximately 18,000 new research papers added each year.

About SPIE

SPIE is the international society for optics and photonics, a not-for-profit organization founded in 1955 to advance light-based technologies. The Society serves nearly 256,000 constituents from approximately 155 countries, offering conferences, continuing education, books, journals, and a digital library in support of interdisciplinary information exchange, professional networking, and patent precedent. SPIE provided more than $3.4 million in support of education and outreach programs in 2014.



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