Neurological research would be greatly assisted if selected groups of cells could be temporarily and safely switched off in a living model. The clinical, behavioural and physiological effects observed would give clues about the function of the silenced cells and their roles in neurological conditions such as epilepsy. In a recent study, scientists at the Massachusetts Institute of Technology, US, discovered a way in which this might become possible.

In science, genes found in one living species (species I) can be made to function in a completely different species (species II). Once the gene has been isolated from species I, it can be 'added' to the nucleus of a weakened virus, which multiplies, producing many copies of the gene. The virus particles can then be injected into a set of cells in species II, taking the gene with them. The gene becomes incorporated into the DNA of the cells and is able to carry out its normal function.

The bacterium, Halorubrum Sodomense, possesses a gene called Arch, which encodes a molecule known as a light-sensitive (i.e. driven by a certain type of light) proton pump (LSPP). Proton pumps are found in many cell types and are responsible for the active (energy-requiring) transport of hydrogen ions (H+) across cell membranes. The movement of H+ into or out of a cell causes changes to the acidity of its environment, which in turn will affect its function. The activity of surrounding cells can potentially be altered also.

In the current study, the researchers inserted Arch into the neurons of a live, awake rodent. The Arch LSPP is driven by yellow light, and when yellow light was shined onto these neurons, nearly all of them stopped functioning (i.e. they switched off). Almost as soon as the light stimulation was removed, the neurons regained their activity. The team observed that the effects of the LSPP were tolerated by the rodent brain, because they were limited to the neurons targeted, without affecting neighbouring cells.

The scientists had, in essence found a safe and reversible way of silencing neurons, in a living, conscious model.

In order to highlight the potential of this tool, the group then repeated the study using a gene known as Mac, found in the fungus Leptosphaeria Maculans. Mac also encodes an LSPP, but this is driven by blue-green light. Again, when blue light was shined onto the neurons, the vast majority switched off. As before, the effects of the LSPP were limited and when the light was taken away, the neurons' function returned.

These findings are very exciting for the future of neurological research. Using LSPPs, scientists will potentially be able to target and silence select populations of neurons, and examine the effects. This will greatly increase our understanding of the function of these neurons, how they work together and their role neurological conditions.

The team in Massachusetts hopes that further study will reveal neuron targets which, when shut down, can provide relief for conditions such as pain and epilepsy. They are also looking to see if the methods used in the current investigation are tolerated in animals more closely related to humans than rodents. If so, in future it might be safe to insert LSPP genes into epileptic neurons in humans. A device could then potentially be developed that detects the start of seizure activity in these neurons, and then shines a specific light onto them to switch them off before the seizure becomes clinical. We look forward to seeing further results from this group.

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