Neurons in this small area in the center of the brain play a key role in keeping in mind information on how to move around in different environments.

MIT Technology Review Italy

As people age, their working memory often decreases, making it more difficult for them to carry out daily activities. A key brain region linked to this type of memory is the anterior thalamus, which is primarily involved in spatial memory and many other executive functions, such as planning and attention.

In a study on mice, which appeared in the Proceedings of the National Academy of Sciences, authors Guoping Feng, Dheeraj Roy and Ying Zhang of MIT have identified a circuit in the anterior thalamus whose improvement greatly increases their ability to perform a maze correctly. In their opinion, intervention in this region could allow therapies to reverse memory loss in older people without focusing, as it is now, on the prefrontal cortex, which has many different functions.

Previous studies in mice have shown that damage to the anterior thalamus leads to impairments in spatial working memory. In humans, studies have revealed age-related decline in anterior thalamus activity, which is closely related to lower performance in spatial memory tasks..

The anterior thalamus is divided into three sections: ventral, dorsal and medial. In a study published last year, Feng, Roy, and Zhang investigated the role of the anterodorsal (AD) and anteroventral (AV) thalamus in memory formation. They found that the AD thalamus is involved in creating mental maps of physical spaces, while the AV thalamus helps the brain distinguish between these memories and others like them.

In this latest research, the authors looked more deeply into the AV thalamus, exploring its role in a spatial working memory task. To do this, they trained the mice to perform a simple T-shaped maze. At the start of each trial, the mice ran until they reached a fork in the road. One arm was blocked, forcing them to move along the other arm. Then, the mice were placed back into the maze, with both alternatives available. The mice were rewarded when they chose the opposite arm to that of the first time. This meant that in order to make the correct decision, they had to remember what they had done previously.

While the mice performed the activity, the researchers used optogenetics to inhibit the activity of AV or AD neurons during three different parts of the activity: the sample phase, which occurs during the first run; the phase of waiting for the start of the second heat and the phase of choice, when the mice decide which way to run during the second race. The researchers verified that inhibition of AV neurons during the sampling or choice phases had no effect on the performance of the mice, but when they suppressed AV activity during the wait phase, which lasted 10 seconds or more, the mice performed much worse in activity.

This suggests that AV neurons are the most important for keeping in mind the information needed for an activity. In contrast, inhibition of AD neurons disrupted performance during the sampling phase but had little effect during the wait phase. This finding is consistent with the research team’s previous study which showed that AD neurons are involved in the formation of memories of a physical space.

“We can talk about two subdivisions within the anterior thalamus,” says Roy, “one that favors contextual learning and the other that actually helps to contain this information”. The researchers then tested the effects of age on this circuit. They found that older mice (14 months) performed worse on the T-maze task and their AV neurons were less excitable, but when the researchers artificially stimulated those neurons, the mice’s performance in the task improved dramatically.

Another way to improve performance in this memory task is to stimulate the prefrontal cortex, which is also subject to age-related decline. However, the researchers found, activation of the prefrontal cortex increases anxiety in mice. They are now planning to perform single-cell RNA sequencing of neurons in the anterior thalamus to find genetic signatures that could be used to identify cells that would be best targets, stimulating them with minimally invasive interventions.

Image by Lisa Van Dorp from Pixabay

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