Many neuroscience studies in animals involve some type of short-term (or acute) manipulation of the brain, followed by behavioral tests. When manipulations of a specific brain circuit are followed by behavioral changes, neuroscientists generally conclude that the circuit contributes to the behavior that's been changed.

But brain circuits are very densely packed and highly interconnected, so it’s hard to manipulate one without influencing others. This makes it particularly challenging to know if the behavioral effects are caused by the part of the brain that was targeted or by some other part that happens to be closely connected to it.

A paper published in Nature shows that short-term alterations and long-term damage can have different effects on behavior. The findings raise a significant caution about the cause-and-effect nature of manipulating the brain and provide a reminder that the brain can sometimes work its way around damage.

These experiments were conducted on songbirds and rats, two common subjects for behavioral neuroscience work. In the rats, the motor cortex of the brain was inactivated, which was intended to change their ability to perform the motor task of pushing a lever. In the songbirds, the researchers targeted a region of the brain that allows these birds to sing courtship songs.

Both the rats and the birds received one of two types of brain manipulations. The first was a transient injection of a drug that deactivates neurons; the drug was injected directly into the region in question. The second was permanent damage to the same brain region, caused by a surgical brain lesion.

After the manipulation, the rats were tested on the same lever-pushing task. Those treated with the drug weren’t able to perform the task well. By contrast, those with permanent brain damage were unable to learn the lever-pushing task. But if they had learned the task before this brain damage, they retained the ability to push the lever.

The songbirds in these experiments were tested for their ability to sing a mating song. Those that had the drug injected were unable to produce songs, but those with permanent brain damage were able to sing again within two days of the brain-altering procedure. Just as with the rats, permanent brain damage had a less severe behavioral effect than the drug injections.

To confirm that these results weren’t an artifact of the drug, the researchers repeated the work using optogenetics, which allowed them to shut down a part of the brain using a beam of light (it was named Nature's "Method of the Year" in 2010). The results were indistinguishable from the drug-induced neuron deactivation.

In these studies, experimental animals that were allowed to sleep after their brains were damaged recovered brain function that was lost in animals who were not able to sleep. This suggests that sleep is important for consolidation of brain activity patterns and for restoration of brain circuitry function. Recovery of function sometimes took days or weeks after the brain damage, which suggested that a spontaneous process was occurring. And since the targeted brain region was completely disabled, recruitment of other regions may be needed for the brain to recover.

The results of this study show that acute changes to the brain may not produce the same effect on behavior as long-term ones, something that should influence how we interpret many experiments. In the process, however, the researchers also learned a bit about how the brain recovers from damage.

These results are consistent with known discrepancies between acute and chronic behavioral effects. Typically, as seen here, acute effects are very severe, but the brain can sometimes recover in time. This is most likely explained by the brain adaptively compensating for functions lost due to damage, a phenomenon known as compensatory plasticity.

Of course, compensatory plasticity can’t compensate for every type of brain damage; the tasks involved in these particular experiments may not be typical. This means that there may be more value in continuing to study differences between chronic and short-term manipulations. In the future, there are sure to be even more studies on the differences between acute and chronic brain damage, which will yield even more insight into these phenomena.

Nature, 2015. DOI: 10.1038/nature16442 (About DOIs).