Biomedical Engineering Reference
In-Depth Information
Halorhodopsin (NpHR) could potentially be used in these cells to restore vision,
because photons naturally cause hyperpolarization of photoreceptors. Interestingly,
expression of NpHR in the inner retinal layer could restore OFF responses, whereas
combined expression of NpHR and ChR2 in RGCs could cause them to respond as
ON, OFF, or even ON-OFF cells depending on the wavelength of light used (Zhang
et al.
2009
). The expression of “enhanced” NpHR (eNpHR) in light-insensitive
cone photoreceptors could substitute for the native phototransduction cascade and
restore light sensitivity in two mouse models of retinal degeneration (Busskamp
et al.
2010
). Importantly, this treatment leads to normal activity in cone photorecep-
tors and RGCs in response to yellow-light stimulation and allows mice to respond
to changes in light intensity and the direction of motion of visual stimulation.
Even in human retinas, eNpHR expression was nontoxic and could rescue light-
insensitive human photoreceptors ex vivo (Busskamp et al.
2010
). These results
demonstrate that optogenetics may be useful for treating various forms of blindness
in humans. Optogenetics may also be utilized to establish various prosthetic devices,
such as specialized glasses that increase light intensity, which have been proposed
to enhance environmental visual stimuli specifi cally for ChR2- or eNpHR-
transduced neurons in the retina (Cepko
2010
).
8.2.2
Refl ex and Innate Behavior
Breathing/Respiration
Brainstem or spinal cord injury may result in paralysis, which leads to the inability
to breathe in severe cases. Although the neuronal mechanism of respiration is not
suffi ciently well understood to restore function to damaged circuits, ChR2-mediated
photostimulation of motor neurons has recently been reported to recover respiratory
diaphragmatic motor activity (Alilain et al.
2008
). In the brainstem, stimulation of
the retrotrapezoid nucleus produced long-lasting activation of breathing (Abbott
et al.
2009a
), whereas stimulation of the ventrolateral medulla increased sympa-
thetic nerve activity and blood pressure (Abbott et al.
2009b
). These studies indicate
that neural and non-neural cell types in the brainstem and spinal cord contribute to
the regulation of a central autonomic process.
Sleep/Wake Circuitry
The sleep/wake cycle is one of the most well-defi ned behaviors whose underlying
principles have been dissected by optogenetic tools. The fi rst use of optogenetics to
study this system used lentivirus-mediated gene delivery to target ChR2 to
hypocretin-expressing neurons in the lateral hypothalamus (Adamantidis et al.
2007
). Dysregulation of the hypocretin system, either of the peptide or its receptor,
