Biomedical Engineering Reference
In-Depth Information
resolution corresponds to a 100-fold loss of axial resolution. A simple solution to
this resolution versus effectiveness tradeoff is to move the stimulation spot very
rapidly across the cell membrane, integrating the cumulative effect of many loca-
tions (Rickgauer and Tank
2009
) for two-photon ChR2 neural stimulation with a
30 ms spiral scan.
To identify functional connections in the real brain, the cell-type- and site-
specifi c causal controls provided by optogenetics and fMRI in mice have been com-
bined to test the linearity of BOLD signals driven by locally induced excitatory
activity (Lee et al.
2010
; Kahn et al.
2011
; Desai et al.
2011
). This strategy helps us
to estimate how linear the response to sensory stimuli is, which is essential for the
design and interpretation of in vivo fMRI experiments.
Additional information about optogenetics, including technical details about
genes and light delivery systems, can be found in other excellent reviews and proto-
cols (Zhang et al.
2006
; Cardin et al.
2010
). More information about available opto-
genetic transgenes can be found at the Optogenetics Resource Center Web page
(
http://www.stanford.edu/group/dlab/optogenetics/
) maintained by the laboratory
of Karl Deisseroth. Details of tools for gene and light delivery are available on the
Web page (
http://syntheticneurobiology.org/protocols
) maintained by the labora-
tory of Ed Boyden.
8.4
Conclusion
Although optogenetics has been established for only 6 years, the number of reports
exploiting these tools is increasing exponentially to provide further answers to ana-
tomical, physiological, and pathological issues. These tools allow us to address the
complexity of neural circuits, for not only in vitro but also in vivo studies. However,
there remains much scope for further refi nement that would allow us, for example,
to stimulate multiple cell types at the same time by introducing various mutations in
a particular domain, as is the case with the multiple available versions of green fl uo-
rescent protein. It will also be desirable to increase the conductance of various chan-
nels so that less light stimulation is necessary, to avoid the expected side effects of
heat on the cell. Finally, it should also be possible to record patterns or sequences of
neural fi ring and then use these recordings to mimic the recorded neural activities
with light pulses. Regarding the therapeutic use of optogenetics, it will be necessary
to develop safe and reversible gene delivery strategies and light delivery devices that
are adaptable to human patients. The use of light to study the brain has proved to be
a remarkably fruitful strategy, and indeed optogenetics has given us a green light for
the future.
Acknowledgements
We thank all members of our laboratories for useful discussion and support.
Fig.
8.1
was adopted from the front page of BioGARAGE, published on March 2012 by Leave a
Nest Co., Ltd. The images in both fi gures were designed by Science Graphics Co., Ltd.
