11.5 Neurophotonics
The basic activities of neuroscientists are to explore and understand the mechanisms
of neuronal activity in the brain [ 30 – 32 ]. A major goal is to develop methods to
control specific classes of excitable neural cells in order to determine the causes and
effects of various diseases caused by malfunctions in these cells. Having a precise
control of specific neural cells would lead to developing treatments for both neu-
ropsychiatric diseases (e.g., Parkinson’s disease, Alzheimer’s disease, pain syn-
dromes, epilepsy, depression and schizophrenia) and non-neural diseases (e.g.,
heart failure, muscular dystrophy and diabetes). Deep-brain stimulation (DBS) with
microelectrodes has been one methodology used in this search. In this technique,
microelectrodes are placed in well-defined anatomical locations for modulation of
neurons in specific regions of the brain. Although these methods alleviated
symptoms in some neuropsychiatric diseases, DBS electrode stimulation causes a
mixture of excitation and inhibition both in targeted cells and in unrelated
peripheral or transient cells.
Subsequently, the ability to precisely control either excitation or inhibition of
neurons was achieved through techniques from neurophotonics [ 30 – 35 ], which
involves the use of photonics in neuroscience research. In particular, the neu-
rophotonics discipline ofoptogeneticsuses opticalfiber links to send light signals to
the brain to control neurons that have been genetically sensitized to light. The basis
of optogenetics is the use of microbial opsins (light-sensitive proteins found in
receptor cells of the retina) that enable neurons to have both the capability to detect
light and to regulate the biological activity in specific targetable molecules. Among
the various opsins used in optogenetics, the two commonly used ones are
channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR). The opsin protein ChR2
activates neurons when exposed to 473-nm blue light and the opsin protein NpHR
inhibits neural activity when it is exposed to 593-nm yellow light. Because the
response spectra of ChR2 and NdHR are sufficiently separated so that they do not
interfere, both can be expressed simultaneously in the same neurons to enable
bidirectional optical control of neural activity.
The optical power used to activate the opsin proteins can come from either a
laser diode or LED and typically is less than 1 mW. If the light has to pass through a
certain thickness of tissue before reaching the opsins then the light attenuation in
the tissue needs to be taken into account. In addition, when light emerges from an
opticalfiber the divergence of the beam depends on the core size and numerical
aperture of the opticalfiber. Opticalfiber core sizes used in optogenetics nominally
range from 100 to 400μm. An online application that can be used to calculate light
transmission through brain tissue can be found on the laboratory website of
Kenneth Diesseroth (http://www.stanford.edu/group/dlab/cgi-bin/graph/chart.php).
This program calculates the spread of the light beam and the depth of penetration
using factors such as the wavelength of light, thefiber numerical aperture, light
intensity andfiber core radius.
334 11 Biophotonics Technology Applications