Working memory usually worsens with age, making it hard to do daily tasks. The anterior thalamus is an important part of the brain because it is mostly in charge of remembering where things are. In a study with mice, scientists at MIT found that a circuit in the front of the thalamus is needed to remember how a labyrinth is set up. Even in older mice, making this circuit work more makes finding your way through a maze easier.
Experts say that this part of the brain may be a good place to treat memory loss in older people without hurting other brain parts. Guoping Feng is a member of the Harvard-MIT Broad Institute and the McGovern Institute for Brain Regeneration at MIT. He thinks that instead of just changing the prefrontal cortex, we might be able to find more precise and druggable targets in this area by learning more about how the thalamus affects the cortical output.
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Today, the Proceedings of the National Academy of Sciences published an essay that Feng helped write. The article talks about how his work made a big difference. McGovern Institute, Broad Institute, and Dheeraj Roy, who got a K99 Award from the National Institutes of Health, wrote the paper (NIH).
Take Note Of Where You’ve Been:
The thalamus is a small area in the middle of the brain that helps with things like working memory and attention. The anterior thalamus, a part of the thalamus that helps with memory and navigation, has been studied by Feng’s group. When the front of the thalamus was hurt in mice, their spatial working memory got worse. People’s ability to remember where things are has been linked to less activity in the front of the thalamus as they age.
There are three parts to the front of the thalamus: the ventral, dorsal, and medial parts. In a study that came out last year, Feng, Roy, and Zhang looked into the anterodorsal (AD) and anteroventral (AV) thalamus. It was found that the AD thalamus is important for making mental maps of places, while the AV thalamus helps the brain tell these memories apart from other memories of similar settings.
Their most recent study tried to find out more about how the AV thalamus works during a test of spatial working memory. Researchers taught mice how to get through a simple T-shaped maze to do this. At the start of each test, the mice ran until they reached the T. Since one arm was blocked, they had to go down the other. The mice went back into the labyrinth, but they went in with both arms open this time. The mice got a reward if they chose the opposite arm from the first run. Before choosing, they had to remember which way they had gone.
This job was done in three steps: sampling, waiting and choosing. During the decision phase, the mice had to choose which method to use to start a second run, while optogenetics stopped AV or AD neurons from firing. When the mice’s AV neurons were turned off for at least 10 seconds during the wait time, they did worse on the test. But this didn’t happen when AV activity was lowered during the sample or choice phases.
It looks like AV neurons remember things best when needed to do something. Stopping AD neurons during the delay phase didn’t change how well they worked during the sample phase. This new research backs up what was found before: AD neurons play a role in remembering places. Roy says that when it comes to learning about space, the ventral neurons seem to be very important during the maintenance phase and the small delay. We now know that the front of the thalamus is split into two parts. One part seems to help with learning about context, and the other seems to help with storing information.
Wear And Tear Caused By Getting Older:
Then, they looked into what time it was on this circuit. Older mice (14 months) did worse on the T-maze task, and their AV neurons were less likely to fire. Researchers couldn’t make the mice do better until they artificially turned on the neurons in their brains.
Even though the prefrontal cortex shrinks with age, it might be possible to stimulate it to improve memory. But researchers found that making the prefrontal cortex work made the mice feel nervous. Zhang says, “If we directly excite neurons in the medial prefrontal cortex, it will also make people act worried, but this won’t happen when AV activation occurs.” Activating the prefrontal cortex in this way is not as good as using AV.
Researchers say that stimulating these neurons in the human brain in a noninvasive or only slightly invasive way may help people keep their memories as they get older. Soon, they want to do RNA sequencing on single neurons in the front part of the thalamus. This will help them find genetic markers that can be used to pick the best cells to use as targets. The Stanley Center for Psychological Research, the Hock E. Tan and K. Lisa Yang Center for Autism Research, and the James and Patricia Poitras Center for Psychiatric Disorders Research at the Broad Institute helped with the research.
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