Scientists discover a deep brain structure crucial for holding thoughts

Reading a sentence, following a conversation, solving a problem or deciding what to do next: all of these rely on working memory. It allows the brain to hold information in mind for a few seconds, even after the stimulus has disappeared, to be able to compare it with new information, manipulate it and use it to guide our behavior. It therefore plays an essential role in the transition from perception to thought, and from thought to action.

UNIGE scientists show that this function relies in part on a small, deep brain structure, the claustrum, whose neurons help keep a trace of information for tens of seconds. Moreover, inhibiting the claustrum leads to a marked drop in working memory performance. These results, published in Nature Communications, add a piece to the puzzle of the circuits underlying thought, a key issue for disorders in which working memory is impaired, notably ADHD and schizophrenia.

Without working memory, it would be difficult to think, understand, decide or adapt our behavior. Indispensable, it is also extremely demanding for the brain. Sensory information vanishes within moments once the stimulus ends, yet its representation must remain stable enough to be used later.

How does the brain manage to retain information that is no longer there? We now know that working memory does not depend on a single brain region, but on the interaction of vast networks involving, among others, the prefrontal cortex, sensory regions, the parietal cortex, the thalamus and other subcortical structures. However, how these networks maintain a representation of information over time remains largely unknown.

To decipher these mechanisms, the teams led by Alan Carleton, Full Professor in the Department of Basic Neurosciences at the Faculty of Medicine, and Ivan Rodriguez, Full Professor in the Department of Genetics and Evolution at the Faculty of Science, set out to explore the role of the claustrum in working memory. This thin structure lies deep within the brain, between the insular cortex and the striatum. "Its neurons are connected to almost all regions of the cortex, which puts it in a good position to receive and influence information from very different networks," explains Alan Carleton.

A trace that outlasts the wait

To test this, the scientists studied mice that received a first piece of information, either an odor or a tactile stimulation. They then had to wait several seconds before receiving a second stimulus and determine whether it was identical to or different from the first one. During this interval, the initial stimulus had disappeared. Yet to succeed at the task, the mice had to keep an internal representation of it.

Our live recordings of claustrum neuron activity showed that a trace of the initial information persisted throughout the entire waiting period. Far from being a static memory, neuronal activity changed over time. Nevertheless, the identity of the stimulus remained sufficiently present to be decoded up to 30 seconds later."

Ivan Rodriguez, Full Professor, Department of Genetics and Evolution, Faculty of Science, UNIGE

Without the claustrum, memory falters

To determine whether this structure is truly necessary for working memory, or merely accompanies it, the scientists temporarily reduced the activity of claustrum neurons. The team notably used optogenetics, a technique that makes certain neurons sensitive to light through specific proteins, allowing their activity to be controlled with an optical fibre at precise moments of the task. When this neuronal activity was disrupted, the mice's working memory performance was halved.

"The result was similar regardless of the type of stimulus, olfactory or tactile, and regardless of when the disruption occurred during the waiting period between the two stimuli," adds Alan Carleton. "Moreover, disrupting the claustrum specifically impairs the ability to use temporarily held information to guide behavior, without affecting perception itself."

What does this mean for cognitive disorders?

Working memory thus relies on the dynamic activity of neuronal networks, which must preserve information while allowing the brain to keep perceiving, thinking and acting. The claustrum plays a central role in this complex architecture thanks to its connections with many of the cortical regions involved.

"Our discovery could help us better understand cognitive disorders in which working memory is impaired, such as schizophrenia or ADHD," explains Alan Carleton. "Identifying the brain circuits that allow information to be maintained over time is an important step towards understanding how these functions can be disrupted. We now need to determine how the claustrum communicates with cortical networks, and how this interaction preserves the fidelity of the representations held in working memory."