Immediate reasoning and behavior depend on a cognitive system of limited capacity and duration, technically called the working memory. Studies have revealed several regions of the brain that process working memory, but the mechanism that enables these scattered regions to interact instantaneously to represent and maintain working memory has been poorly understood.

Neuroscientists at the Sainsbury Wellcome Centre at the University College London (UCL) and the University of Basel have investigated visual working memory in mice using optogenetics to discover that the distributed representation of visual working memory is dependent on high-dimensional instantaneous reciprocal interactions between two distinct regions—the parietal and premotor cortices—in the neocortex of the brain. These findings were published in an article titled, “Cortical feedback loops bind distributed representations of working memory,” in the journal Nature.

“There are many different types of working memory and over the past 40 years scientists have been trying to work out how these are represented in the brain,” said first author of the study, Ivan Voitov, PhD, a research fellow in the laboratory of Thomas Mrsic-Flogel, PhD, a professor and director of the Sainsbury Wellcome Centre for Neural Circuits and Behavior at UCL. “Sensory working memory in particular has been challenging to study, as during standard laboratory tasks many other processes are happening simultaneously, such as timing, motor preparation, and reward expectation.”

Mrsic-Flogel said, “By recording from and manipulating long-range circuits in the cerebral cortex, we uncovered that working memory resides within co-dependent activity patterns in cortical areas that are interconnected, thereby maintaining working memory through instantaneous reciprocal communication.”

In this study Voitov and Mrsic-Flogel compared the neural workings of visual working memory in mice engaged in two alternating tasks—one that required working memory and one that did not.

The working memory task required mice to match an image to one they were shown a short while ago to win a treat, reasoning that during the short delay (0.4 to 0.8 seconds) between the two images, mice must hold the first image in their working memories. In the simple discrimination task that did not require working memory, the decision the mice made following the second stimulus was unrelated to the first.

Comparing neural activity in these two tasks enabled the scientists to distinguish those areas of the brain that were required for working memory from those that were simply required for activity in the test environment.

They found working memory representations were embedded within a combination of subtle fluctuations of the mean firing of individual cells that the authors call “high-dimensional” modes of activity. Indeed, most neural activity was “low-dimensional” and unrelated to working memory. Shared modes of neural activity in both tasks challenge the notion that low-dimensional common activity during the delay represents the working memory, and instead suggest that it reflects common task attributes such as the timing of the task, motor preparation, or reward expectation.

The authors then used optogenetics—the use of specific wavelengths of light to control neuronal activity—to selectively silence parts of the brain during the delay period between the two visual stimuli and noted how this affected working memory.

They found that silencing either the parietal or premotor cortical areas led to similar deficits in working memory. This suggested that the representations of visual working memory in these two areas were co-dependent instantaneously during the brief gap between the first and second stimuli.

In future studies, Voitov and Mrsic-Flogel plan to study patterns of neural activity in mice that are shared between the parietal or premotor cortical areas. They will design working memory tasks with distractors between the two stimuli to introduce a bias. This will enable them to not only quantify the strength of working memory, but also modulate the specific information being stored.

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