Neuronal light switches


The September issue of Scientific American contains an excellent and lengthy article about a state-of-the-art technique called optogenetics, by molecular physiologist Gero Miesenböck, who has been instrumental in its development.

As its name suggests, optogenetics is a combination of optics and genetic engineering. It is a powerful new method for investigating the function of neuronal circuits, based a number of light-sensitive proteins which have recently been isolated from various micro-organisms.

By fusing their genes to promoters which control where they will be activated, researchers can target the proteins to specified cells and thus render those cells sensitive to light. Importantly, each protein is sensitive to a specific wavelength of light and responds to it by changing its three-dimensional structure so that ions can flow into or out of the cell. This conductance can either increase or decrease the electrical activity of the cell, depending on the species of ion and the direction of the flux.

The activity of cells expressing these proteins can therefore be controlled by laser pulses. Individual cells can be made to express combinations of proteins, each sensitive to a different wavelength of light, so that, for example, blue light activates and red light inhibits neuronal activity. This control is remarkably precise - it can be achieved on a millisecond-by-millisecond timescale, such that a single action potential from a train of impulses can be eliminated.

In his article, Miesenböck describes how he and others developed optogenetics from existing techniques which use fluorecsent proteins as cellular dyes. He then discusses the work of a number of researchers who are applying the method to investigate how circuits of neurons generate simple behaviours, and goes on to look at its potential medical applications.


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