Optogenetics: Lighting the way for the future
Optogenetics is an intricate yet beautifully simple technology that has transformed the work of scientists in over 800 laboratories around the world since 2005 when the full potential of microbial-opsin optogenetics was first realised.
Hailed as 'Method of Year' in Nature Methods in 2010, and 'Breakthrough of the Decade' by Science, optogenetics is a single-component control strategy that enables fast, precise, defined control of complex biological systems.
Put simply it is a combination of genetic and optical methods to exert control over targeted cells within living tissue; this control can be milli-second precise and cell type specific. It allows deeper analysis of biological systems through the precise manipulation of electrical and biochemical activity within individual cells without disturbing wider processes in the tissue or organism.
Francis Crick in 1979 had first hypothesised that progression of neuroscience was limited by our inability to independently control one type of cell, while others were unaffected, and suggested light may be the right tool. As far back as 1971 microbial biologists had identified the presence of light-activated proteins that control transmembrane ion flow and subsequently influence excitation or inhibition of cells. However it wasn't until 2005 in Karl Deisseroth's lab in Stanford that the microbial opsin, channelrhodopsin (ChR2), from unicellular algae was successfully introduced to mammalian studies and demonstrated millisecond-scale temporal, causal control of function in living cells.
Optogenetics has rapidly become a prominent tool for neuroscientists and has spurred on developments in associated enabling technologies to meet the demand of the growing market. Just a few simple stages are required to successfully control cellular function via optogenetics beginning with the presence of light-sensitive proteins either naturally occurring or genetically introduced to a biological system. Spatially targeted and temporally controlled illumination is then required to activate the microbial opsins which will modulate the membrane potential or cell's signalling. Broadly speaking there are two classes of microbial opsin which can be used to investigate neuronal systems; the channelrhodopsins which excite neurons by causing depolarization when exposed to blue or red light and halorhodopsins which inhibit action potentials in response to yellow light.
The emerging range of Light-emitting diode (LED's) products are rapidly becoming the first choice for researchers in place of conventional discharge and incandescent lamps in microscopy and when using optogenetic techniques. LED's offer a cost effective, application specific tool for illumination. An LED can produce narrow wavebands of light at a specified wavelength with the ability to switched on/off instantly. They also require no warming up or cooling down period, offering consistent illumination throughout the time it is switched on and it's whole lifetime, as well as the advantage of remaining at a low temperature throughout. These qualities make the LED's a perfect partner for optogenetics.
The final stage in optogenetic control is to record the effects illicited by illumination of the photosensitive proteins. This can be done in a number of ways from comparatively primitive electrode recordings of membrane potentials to behavioural studies of free moving animals.
The vast range of applications for optogenetics generates an equally impressive array of illumination hardware required to deliver the required illumination. These range from single wavelength LED's which couple with optical microscopes to miniaturised LED's for targeting specific cell types deep within the brain on freely behaving animals.
It is clear to see that optogenetics will continue to be an invaluable tool for expounding our understanding of complex biological functions; it is also exciting to realise that optogenetics is still in it's relative infancy and the casual control it offers for targeted small-scale events has limitless possibilities for future biological and medical advances.
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Image credit: The Jackson Laboratory