It takes a sizable powerhouse for the human brain to create and support memory, and the gears go to work each time we recall a particular memory, making a new one each time. Crucial to this infrastructure is a small region in the brain known as the anterior thalamus – a bundle of nuclei that receive input from the cerebral cortex while limiting input from the hippocampus. One of the anterior thalamus’ primary connectors is the mammillothalamic tract (MTT), and damage to it has been known to cause memory loss in stroke victims, trauma that many experts have up until this point suspected was irreversible.
A new study, however, released in November by the journal Current Research in Neurobiology, published by Elsevier, consisting of international research conducted by the Universities of Canterbury and Otago, in New Zealand, in collaboration with the University of Oxford, in the UK, suggests a new path forward. With therapeutic stimulation of the anterior thalamus, the researchers were able to not only increase the degree of memory-related brain activity, but also restore the functions of memory in lab rats who had MTT lesions. These findings are welcome news for potential therapies that make use of targeted stimulation of the anterior thalamus – and give new hope to patients suffering from memory loss due to brain injury.
Prof. John C. Dalrymple-Alford is a world-renowned expert in anterior thalamus research and served as the study’s lead investigator. As a neuroscientist, he has spent a career trying to restore lost functions of the brain after they disappear, a goal he shares with many of his colleagues. Memory loss, however, is the one that has intrigued him the most, with the complexity of its nature: “Memory loss can be caused by damage to one or more key points in a distributed memory system. Such damage occurs in several neurological conditions—acute brain injury, such as that caused by a stroke, and in dementia—and affects the quality of life of patients.
“Given how complex the brain is, we are yet to fully understand whether memory impairments are caused by irreversible tissue loss, or by dysfunctions in the wider brain network. Through this study, we wanted to shed light on the latter and understand whether lost memory function, seemingly gone forever, could be retrieved.”
For many years, it was believed that brain cells that are destroyed cannot be replaced, and that the brain only has elasticity to a point – that there were limits to what it could absorb. New discoveries on the brain’s mechanisms have come to challenge these long-held beliefs and opened the door to finding new treatments that were once the stuff of science fiction. In order to test their proposed hypothesis, Prof. Dalrymple-Alford and his team of researchers first recreated memory loss in a group of lab rats by propagating MTT lesions in these rodents, citing the known relationship between damage to the MTT and the onset of memory loss in humans.
Afterwards, they studied the impact of these lesions on the brain’s spatial memory—the way in which the brain commits different places to memory – (it’s the reason why you’re always able to navigate your living room in the dark)— with the use of a radial arm maze (RAM) test. Through their observations, the research team found evidence indicating that these MTT lesions made it more difficult for the affected rats to find their food pellets in the maze, suggesting a degraded working memory and the onset of amnesia-like symptoms.
The next step for the researchers was to test whether or not it was possible to restore working memory in the rodents with MTT lesions. Based upon previously uncovered evidence that an active involvement of the anterior thalamus in the support of memory and a strong correlation between both the brain’s anterior thalamus and the MTT, the researchers then proposed whether an active stimulation of the anterior thalamus could help the brain’s overall memory function better. Next in the mix was optogenetics, which is a light-based technology for controlling the activation of targeted neurons. Using light signals, they stimulated the anterior thalamus neurons in the rats afflicted with MTT lesions and then gave them the RAM test once again.
This time, the rats overall did a considerably better job at retrieving their food pellets in the maze, indicating the stimulation’s benefit on their spatial working memory, even if the improvements were only temporary. It also improved the electrical rhythms moving throughout the brain’s memory system, a surprising side effect that Dalrymple-Alford’s team did not anticipate. The light stimulation also caused an increase in the brain’s expression of a protein called Zif268—which neuroscientists cite as an indicator of high neural activity—throughout the memory system. Interestingly, when they tried to apply the same stimulation based to the hippocampus, which researchers have long considered to be the crux of maintaining spatial memory, there was no memory-enhancing effect on the rats with MTT lesions.
This is the first study to demonstrate that it is possible to improve working memory even after there has been considerable permanent damage done to the brain’s MTT. Pieced together, the team’s body of findings mount a challenge to age-old notions that the retrieval of memory is heavily indebted to regions of the brain such as the hippocampus and prefrontal cortex, suggesting the process of creation is even more fluid that we’ve suspected all along. Even more important, this study offers neurobiologists the first solid piece of evidence implicating the function of increased neuronal activity inside the anterior thalamus as essential in supporting memory.
Beyond just acting as a communication structure, these specialized nuclei serve an active and continuous role in maintaining both our memory and our cognition. Their findings clearly demonstrate that an efficient degree of stimulation to the anterior thalamus neurons can help to counter conditions such as clinical amnesia – a condition associated with obstructions of neural pathways involving the MTT. From there, it’s not a far leap to find new out of the box approaches to disorders beyond brain injuries or stroke – potentially slowing down the onset of conditions such as Alzheimer’s disease or schizophrenia. Should this prevail in clinical tests on human patients, it could make a considerable difference in combination with other stimulation therapies on the brain.
According to Prof. Dalrymple-Alford’s observations: “So far, the hippocampus and prefrontal cortex have remained the focus areas for memory-related therapies. Our study shows that structures outside these areas, such as the anterior thalamus, could instead hold the key for such treatments. It is important to remember that such stimulation does not affect the content of the memory; instead, it appears to enhance the functionality of the brain’s memory system. This could minimize brain impairments and allow patients to live a normal life. While the model we used in our study is typically observed in adult patients, similar injuries could be involved in childhood amnesia. The applications of our findings could have an even greater impact in these patients.”
