I'm back, after an extended hiatus due to my big move to Chicago to
begin grad school. I’ve been
pummeled by work for the past month, so I’ll keep this one short and sweet.
The future is here!
We can manipulate the nervous systems of living beings with focused
beams of electromagnetic energy. This
new trick has been termed optogenetics: the optical manipulation of genetically
altered cells. The journal Nature Methods chose optogenetics as
their 2010 method of the year because previous techniques for exploring the
nervous system, like the application of drugs or electrical shocks, are much
less spatiotemporally precise than a light pulse. This novel method allows researchers to
perturb individual neurons on millisecond timescales with micrometer-level
precision and may help decode the mysteries of learning, memory, sleep, and
other complex neurological phenomena.
The way it works hinges, as usual, upon our friends, the
microbes. A class of membrane-spanning
ion channels and pumps called opsins are responsible for the light-induced
activation/repression of neuronal activity.
Channelrhodopsins (ChR) - light-activated ion channels - are used to
depolarize (activate) neurons, while halorhodopsins can be employed to hyperpolarize
(inhibit) neuronal firing by pumping anions into the cell using light
energy. These microbial proteins are
inserted into particular invertebrate (nematode and fruit fly) and vertebrate
(mouse) neurons or muscle cells via genetic engineering.
Recently, in Nature
Methods, Stirman et al. (2011) designed a clever optical set-up, using
custom modifications to a commercially available Hitachi 3-LCD projector (see below)
to perturb microscopic light-sensitive samples with a high degree of precision. Using the
software program LabView, they programed the microscope stage and the projector
to track a moving nematode while shining light on a defined patch of the worm’s
surface. This tool is two orders of
magnitude cheaper than current conventional systems, which are available for
this same type of work. This levels the
playing field for labs with limited resources by allowing them access to this cutting-edge methodology.
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| Figure 1 (a,b and c) from Stirman et al., 2011. Pannels a an b show the optical set up for the microscope and the projector. Pannel c shows different illumination schemes that were developed for manipulating light-sensitive nematodes. |
My biophysical colleagues and I are attempting to build our
own custom version of the optical set-up in Stirman et al. (2011) and engineer
new strains of optogenetically sensitive mutant worms. While this is part of a required lab course,
we plan to run new experiments that can be turned (fingers crossed) into a publication. Really, we just want to make worms
dance. Our ultimate success would be to
choreograph a music video of “Bad Romance” by Lady Gaga, using an all-nematode
cast. Stay tuned, science fans.
Stirman, J., Crane, M., Husson, S., Wabnig, S., Schultheis, C., Gottschalk, A., & Lu, H. (2011). Real-time multimodal optical control of neurons and muscles in freely behaving Caenorhabditis elegans Nature Methods, 8 (2), 153-158 DOI: 10.1038/nmeth.1555
