. Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy. Nat Med. 2011 Feb;17(2):223-8. PubMed.


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  1. Imaging calcium signals in neural structures like cortex are currently the only way to detect the activity of many or most neurons in a volume of tissue. Clay Reid in the Neurobiology Department at Harvard Medical School did this a while back and made important discoveries about the functioning of visual cortex. The current system, developed by Katsushi Arisaka, is a clever way to improve on the original method that Reid used. Basically, the idea is to use multiple lasers (four in this case) to make multiple (four here) simultaneous images. This lets you look over a larger volume of tissue or with better temporal resolution. This microscope is a technological tour de force and effectively pushes the limits of this approach.

    I am confident that there will be important special uses for this instrument. There are several limitations of the two-photon microscope, however, and this advance improves on one of them (making a larger or faster image), but not on the other (maximum depth in cortex that can be studied is only about 0.4 mm, whereas the cortex is at least 1 mm thick). Furthermore, although the fourfold speed increase is impressive, something like a 10-fold increase—or 100-fold—is what you really would want. So this is a wonderful technological achievement that will be important, but it is not a "game-changer."

    View all comments by Charles Stevens
  2. This is lovely technology with promise for future important biological studies
    and represents one of a series of technical improvements in multiphoton
    microscopy that allow deep imaging (e.g., with GRIN lenses) or use of awake,
    behaving animals. Along with the exciting new opticogenetic reagents, we are a
    step closer to being able to use optical tools to monitor neuronal activity in
    populations of neurons during normal behaviors and under disease conditions.

    View all comments by Bradley Hyman

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