Meet the region of the brain that may control your consciousness

For such a wispy, diminutive region of the brain, the claustrum has been the subject of some audacious speculation. The most remarkable came from Francis Crick, of DNA double-helix fame, and renowned neuroscientist Christof Koch: they speculated that the claustrum, which is located deep within the brain structure, might be the seat of consciousness, likening it to a conductor of an orchestra. This theory had never been proven. But now, a mouse study by an all-RIKEN team of neuroscientists has shown that the pair was partly right.

The study observed that optogenetic (light) activation of the claustrum silenced neurons in the brain’s cortex, the outer ‘grey matter’ part of the brain linked to many higher functions. Moreover, this silencing is characteristic of the brain’s slow waves that occur in deep sleep just before rapid-eye-movement (REM)sleep. These waves have been linked to brain-wide synaptic homeostasis and memory consolidation.

The name claustrum derives from the Latin word for a locked or enclosed place. It’s an appropriate name, because while neuroscientists have known about the claustrum for a long time (as a brain region hidden beneath the cerebral cortex) they have been unable to pin down its role. Its wispy, nebulous structure makes it difficult to access and manipulate.

Although the claustrum’s function remained elusive, researchers had been able to determine its structure. They found that it has a characteristic ‘crown of thorns’ structure that makes connections with almost all areas in the neocortex, the area of the brain responsible for a diverse range of functions, including sensory perception and cognition.

Yoshihiro Yoshihara of the RIKEN Center for Brain Science never set out to investigate the claustrum; rather he stumbled upon it while he and his team were studying the neuroscience of smell. This research involved genetically manipulating mice so that certain neurons along the olfactory circuit that initially processes smell signals from the nose can be visualized and activated by light.

But in one line of transgenic mice the manipulation was not expressed in the target neurons. “The technician who screened the transgenic mice came to my office and told me that the transgene, Cre recombinase, wasn’t expressed in smell-related neurons in these mice, but in an unknown region,” Yoshihara recalls. “And she asked if we should discard these mice.”

After poring over images of the mice’s brains and consulting a brain atlas, Yoshihara came to a startling realization—the transgene was expressed only in the claustrum. “I told the technician, ‘Whatever you do, don’t discard that line! It could be a vitally important resource for neuroscience.’”

This line of mice provided Yoshihara’s team with the key for unlocking the claustrum, since for the first time they could genetically visualize, activate and ablate (remove) neurons in the claustrum alone.

They were surprised when they tried optogenetic activation. “When we activated claustrum neurons by light, we observed total silencing of cortical neurons for more than a tenth of a second—a very long period,” says Yoshihara. “I was very excited when I saw the data and felt we had probably found a very important and interesting result for neuroscience.”

The extended period of silence is a characteristic of slow waves in the brain, which occur during the deep sleep that precedes rapid-eye-movement sleep. Thus, the observation that exciting neurons in the claustrum induces silences was clear evidence that the claustrum is responsible for coordinating slow-wave activity in the cortex.

“The critical finding is that the claustrum coordinates cortical activity very broadly in widespread areas—and that’s something that only claustrum neurons can do,” says Yoshihara. “This is highly significant not only for sleep research but also for research into higher brain functions.”

Yoshihara notes that the finding partially vindicates Crick and Koch, but that it also differs in at least one important respect. “They thought that the claustrum probably activates cortical neurons globally, but our result is the opposite—the claustrum inhibits or silences cortical neurons globally.”