Nom original: 0054.pdf
Ce document au format PDF 1.4 a été généré par TeX / MiKTeX pdfTeX-1.30.6, et a été envoyé sur fichier-pdf.fr le 13/10/2011 à 03:17, depuis l'adresse IP 92.162.x.x.
La présente page de téléchargement du fichier a été vue 851 fois.
Taille du document: 1 Mo (3 pages).
Confidentialité: fichier public
Télécharger le fichier (PDF)
Aperçu du document
The neurophotonic interface:
stimulating neurons with light
Nir Grossman, Konstantin Nikolic, and Patrick Degenaar
Remote neural control is performed with single-cell single-actionpotential resolution.
At the end of the 18th century, Luigi Galvani demonstrated that
nerves could be excited with electrical stimuli. Since then, scientists and engineers have been working on the development of
neuroelectronic interfaces such as those popularised in the fictional works of Mary Shelley (Frankenstein) and William Gibson (Neuromancer). Despite advances in the miniaturization of
electronics, materials science, and stimulation biophysics, neuroelectronic interfaces suffer from many fundamental drawbacks.
These include the following: poor spatial resolution, since the extracellular microelectrodes typically used today simultaneously
interface with all neurons within approximately 100µm; poor selectivity, as it is not possible to preferentially stimulate specific
neurons; and non-flexible electrode-neuron contact. In addition,
this kind of stimulation is invasive.
In 1971 Richard Fork showed that a high power laser can
stimulate neurons by physically punching temporarily holes in
their membranes. Equally, ultraviolet- (UV-) activated release of
caged neurotransmitters to stimulate neurons was developed in
the 1970s.1 However, the real excitement began in the end of
2003 when Peter Hegemann’s group from the Max-Planck Institute for Biophysics discovered a light-activated ion channel in a
swamp algae. This ion channel, called the ChannelRhodopsin-2
(ChR2), is the first light-activated ion channel that can transport
the sodium and calcium ions necessary for neuron stimulation.2
Since then there has been a race to genetically engineer this ion
channel in animal cells, resulting in around 40 papers in just the
last 12 months.2 The field is now moving from genetics to biophysics and bioengineering.
The neurophotonics interface
Our group is mainly interested in using this ion channel as a
novel type of neurointerface based on light instead of electricity.
We use special custom-made light-emitting-diode (LED) matrix
to stimulate multiple neurons in parallel. The micro-LED array
Figure 1. Light from a micro-LED stripe triggers action potentials in a
ChR2-transfected neuron with single-cell single-spike resolution.
we currently use is based on Gallium Nitride (GaN) technology.
It emits 470nm blue light, which matches the absorption peak of
In our first set of experiments we used the LEDs to stimulate action potentials in rat hippocampal neurons photosensitized with ChR2.3 We recorded the responses from single cells
with a standard patch-clamping technique and, using the unique
spatiotemporal resolution of the micro-LED array, succeeded in
stimulating an arbitrary combination of neuron cells and a single
cell with sub-cellular resolution. We believe this is the first such
demonstration. Figure 1 shows a single blue micro-LED stripe
illuminating the body (soma) of a ChR2 transfected neuron (the
ChR2 is coupled to yellow fluorescence protein and therefore
has a green fluorescenting appearance). The inset on the bottomleft shows the neuron response (white) to a train of four light
Continued on next page
10.2417/1200802.0054 Page 2/3
Figure 2. Microscope image of a blue 64 by 64 matrix light emitting
diode where 2 rows of LEDs are turned on. The scale on the top image
is 200 microns
pulses (10ms pulse duration) at a frequency of 10Hz. We showed
that single action potentials could be accurately and reliably triggered up to a frequency of 40Hz.
The initial array that we developed consisted of 120 microstripes,3 but we are now moving to matrix arrays of 64×64 pixels (20µm radius; 50µm pitch) that can be flip-chip bonded to
complimentary-metal-oxide-semiconductor (CMOS) controllers
(see Figure 2). The CMOS control is particularly exciting as it
allows us to implement independent oscillator control of the individual pixels rather than raster scanning.
There are many advantages in using light to interface with
neurons. The technique has micron spatial resolution and millisecond temporal resolution. It has flexible ‘electrode’-neuron
connections, high specificity (by targeting the expression of
ChR2) and offers a remote (non-invasive) control of neural activity. Moreover, another recent exciting discovery has been
HaloRhodopsin, which can be used to optically inhibit action potentials. Thus, while we are still largely at the biophysics stage,
the field will soon be transferring out to neuroscientists, bioengineers, and neuromorphic engineers. It will then become a
very important tool for probing brain function, and for developing novel prostheses such as those for the retina.4 It may even
be possible to have an optical link between biological and silicon components in a hybrid neurocomputer: this would present
many interesting possiblities.
The objective of our own work is to develop a neurophotonic
visual prosthesis. Electronic retinal implants have not been able
to follow in the footsteps of cochlear implants, largely because
of the high power consumption required for stimulation (10µW
is acceptable if you need 16 electrodes for a cochlear implant but
becomes problematic if you require 500-10,000 which is the minimum requirement to return the most rudimentary vision). Photonic stimulation would allow the system to be non-invasive,
and keep all the power requirements external, thus massively
There are, however, several issues that need to be addressed
before the neurophotonic interface can be fully functional. The
kinetics of the triggering process and its side effects on the neuronal response must be better understood. Additionally, for our
own purposes, we want to bring the stimulation requirement for
the ChannelRhodopsin down so that we can reduce the power
consumption of the final prosthesis. Nevertheless, the future
The authors would like to express a special thanks to the researchers
of Mark Neil’s group at the Physics Department, Imperial College, for
their invaluable help in the development of the interface. Special thanks
too to Juan Burrone’s group from the Medical Research Council’s Centre for Developmental Neurobiology at King’s College London for the
neuron stimulation experiments. Our work was funded by the Royal
Nir Grossman and Patrick Degenaar
Institute of Biomedical Engineering and
Department of Neuroscience
London, United Kingdom
Institute of Biomedical Engineering
London, United Kingdom
Continued on next page
10.2417/1200802.0054 Page 3/3
1. E. M. Callaway and R. Yuste, Stimulating neurons with light, Curr. Opin. Neurobiol. 12 (5), pp. 587–92, 2002.
2. F. Zhang et al., ChannelRhodopsin-2 and optical control of excitable cells, Nature
Methods 3 (10), pp. 785 – 792, October 3 2006.
3. V. Poher, N. Grossman, et al., Micro-LED arrays: a tool for two dimensional neuron
stimulation, J. Phys. D. (Accepted for publication.)
4. P. Degenaar, M. W. Hankins, E. Drakakis, C. Toumazou, C. Kennard, K. Nikolic,
and H. Yan, Rentinal Prosthetic devices, Patent WO20, pp. 0714 – 8038.
c 2008 Institute of Neuromorphic Engineering