Sara Reardon in Nature:
In the tightly woven networks of the brain, tugging one neuronal thread can unravel numerous circuits. Because of that, the authors of a paper1 published in Nature on 9 December caution that techniques such as optogenetics — activating neurons with light to control brain circuits — and manipulation with drugs could lead researchers to jump to unwarranted conclusions. In work with rats and zebra finches, neuroscientist Bence Ölveczky of Harvard University in Cambridge, Massachusetts, and his team found that stimulating one part of the brain to induce certain behaviours might cause other, unrelated parts to fire simultaneously, and so make it seem as if these circuits are also involved in the behaviour. According to Ölveczky, the experiments suggest that although techniques such as optogenetics may show that a circuit can perform a function, they do not necessarily show that it normally performs that function. “I don’t want to say other studies have been wrong, but there is a danger to overinterpreting,” he says.
Ölveczky and his colleagues discovered these discrepancies by chance while studying rats that they had trained to press a lever in a certain pattern. They injected a drug called muscimol, which temporarily shuts off neurons, into a part of the motor cortex that is involved in paw movement. The animals were no longer able to perform the task, which might be taken as evidence that neurons in this brain region were necessary to its performance. But Ölveczky accidentally damaged one animal’s motor cortex while injecting the drug. He decided to use a toxin to permanently destroy that portion of the brain to see whether such a lesion would have the same effects as the temporary disruption. When the researchers tested this rat ten days later, they were surprised to find that it could still press the lever correctly, despite having not performed the task since the damage occurred. The observation suggested that the damaged circuit was never actually involved in the behaviour in the first place; without practice, the brain cannot simply switch to using a different circuit. The researchers concluded that their muscimol experiment had shut down multiple circuits, some of which were involved in the lever-pressing behaviour.