We Finally Know What the Claustrum Does

Three years ago, I asked what this brain region does. Now, we know the answer.

Posted Nov 11, 2020

Timothy Dykes/Unsplash
Source: Timothy Dykes/Unsplash

Three years ago, I asked, “What the heck is a claustrum?” In that post, I described the mystery of this oddly shaped brain region, located just below the cerebral cortex. Because the claustrum is vanishingly thin in its cross section (think of a pancake shaped like North America), very few patients or lab animals have experienced lesions that specifically destroy the claustrum. For this reason, it’s difficult to pin down what happens when just this brain region (and not others) goes offline. But given its wealth of connections to other brain areas, neuroscientist Christof Koch speculated in 2017 that “the claustrum could be coordinating inputs and outputs across the brain to create consciousness.” This idea is supported by a report of a woman with epilepsy who lost consciousness after her claustrum was electrically stimulated, and perhaps also by the consciousness-transforming effects of Salvinorin A, a drug that binds to receptors that are abundant in the claustrum and alters body image. Could the claustrum, an enigma of the brain, also be the key to the conscious mind?

Well, now we have the answer. Using a genetic engineering technique called optogenetics that enables neurons to fire impulses in response to blue light, a team at the RIKEN Brain Science Institute in Japan has discovered what the heck the claustrum actually does. During deep sleep when you’re not dreaming, your cerebral cortex shows slow waves of electrical activity. These waves are very synchronous, meaning they reflect the coordinated activity of many neurons, more so than the smaller, faster waves that are generally present when you are either awake or dreaming. How does the brain coordinate the activity of so many neurons? It turns out that the claustrum plays a key role.

Stimulating the claustrum in mice using blue light causes inhibitory neurons to fire elsewhere in the cortex. These inhibitory neurons silence other neurons, and they do so in a synchronized manner, acting together all at once to create large, slow waves of electrical activity. In fact, stimulating the claustrum in this manner leads to a state of silence across the cortex, called a down-state, in which many neurons are quiet and unresponsive. This occurs at the bottom, or trough, of each slow wave. Little, if any, information processing can occur during a down-state. And when information processing goes offline, the conscious mind vanishes, as occurs each night during dreamless sleep. This occurs at the bottom, or trough, of each slow wave. And when information processing goes offline, the conscious mind vanishes, as occurs each night during dreamless sleep.

Just to make sure they really understood what the claustrum does, the team at RIKEN next decided to destroy the claustrum in mice. Remember that the claustrum is especially difficult to lesion due to its odd shape? The researchers got around this by genetically engineering neurons in the claustrum to express a receptor for a toxin. This toxin was then injected into the claustrum, destroying its neurons. The result? Slow waves disappeared, though not completely everywhere. The effect was strongest over frontal cortex, suggesting that the neurons which were destroyed by the toxin may have been better connected to the frontal cortex than other regions. If all neurons in the claustrum were destroyed by the toxin, the effect on slow waves would probably have been the same in all cortical regions.

According to Yoshihiro Yoshihara, senior author on the study published in Nature Neuroscience in May, successfully engineering mice that would express certain receptors only in the claustrum was an unforeseen feat. “I was very surprised when we serendipitously generated the transgenic mice expressing Cre recombinase specifically in the claustrum,” he told me. “I was much more excited when we found that the optogenetic stimulation of the claustrum induced global silencing [a down-state] of the cortical neurons.” At last, it appears that a long-standing mystery in neuroscience has been solved using optogenetics. So that’s what the claustrum does.

This post also appears on Knowing Neurons.

References

Narikiyo, K., Mizuguchi, R., Ajima, A., Shiozaki, M., Hamanaka, H., Johansen, J. P., ... & Yoshihara, Y. (2020). The claustrum coordinates cortical slow-wave activity. Nature Neuroscience, 1-13.