Thalamus regulates adult brain plasticity: Study

Scientists discovered that the thalamus, which acts as a relay station for incoming sensory and motor information, plays an unexpected role. The cortex is commonly regarded to have a significant part in the adult brain's ability to adapt.

"This could be an interesting starting point for various therapies," Christiaan Levelt speculates.

To learn new things, our brains must have a large amount of processing capability. The term "plasticity" refers to how our brain adapts to new experiences. Critical periods in human development are times when brain networks are very flexible. However, the adult brain may adapt as well. It is unclear where this plasticity occurs in the adult brain. Under the direction of Christiaan Levelt, Yi Qin and his associates investigated the mouse visual system to learn more about this issue. Due to its simplicity of manipulation, this model is a favourite for research on plasticity.

The retina sends visual information to the thalamus. The visual cortex receives processed information from this brain region and vice versa. An experiment on mice can plainly show how adaptable the adult brain is. The visual cortex of the mouse begins to respond less effectively to the closed eye and more efficiently to the open eye after several days of occlusion of one eye. For a very long time, it has been unclear how exactly this is governed.

But these new results bring an important player to the forefront: the thalamus.

Christiaan Levelt said, "Five years ago, we discovered that the thalamus plays a crucial role in the plasticity of the visual cortex during critical periods of development. This has changed our perspective on how this whole system works. We all thought that this process was regulated by the visual cortex, but it turned out not to be the whole story."

"We found out by removing a very specific component, the GABA-alpha 1 subunit, in the thalamus of mice during their critical period for vision. This component is responsible for inhibiting the thalamus, so its removal resulted in reduced inhibition. When we closed one eye in these mice, the shift in responses no longer occurred. Because the adult brain uses different plasticity mechanisms than the developing brain, an important question was whether adaptation in the adult visual system also involved the thalamus".

Yi Qin said, "In the current study, we performed the same experiment in adult mice and observed similar results. We observed that plasticity also took place in the adult thalamus, but disappeared when we removed the alpha-1 subunit. Consequently, there was no longer a shift in the cortex either. Since we know that the visual cortex also sends information back to the thalamus through a feedback mechanism, we were curious if the visual cortex also plays a role in the plasticity of the thalamus."

"We investigated this by reversing the experiment and shutting down the visual cortex. What happens to the shift in responses in the thalamus then? In adult animals, we did not see any difference: the shift persisted. However, in animals during their critical period, we observed that when we shut down the visual cortex, the shift reverted back to the thalamus. So, at a young age, plasticity in the thalamus and cortex influence each other much more, while in the adult brain, the thalamus is particularly important for plasticity in the cortex but not the other way around."

Levelt continued: "Plasticity is important in many processes. We are currently focusing on sensory plasticity (vision), but plasticity is also fundamental for memory and other functions. These new insights could be relevant, for example, in understanding learning disabilities. It is possible that the origin of these problems lies in the thalamus rather than the cortex."

"Therefore, a different approach is needed. Instead of solely looking at the cortex, we should also consider the thalamus when it comes to therapies and the pathogenesis of these issues. This is an important new interpretation.

Qin said, "Even in the case of lazy eye, it is assumed to be a problem of the cortex, but it could also involve the thalamus. In Europe, we test for the presence of lazy eye from a young age. This condition can be corrected during the critical period by temporarily patching the 'good eye,' which strengthens the connections to the weaker eye."

"In the US, for example, this is not routinely checked at a young age, resulting in more people carrying a lazy eye into adulthood. Since the critical period has already passed for them, it becomes more challenging to treat these individuals. Our study provides a hint that we need to look beyond the cortex, which can provide guidance for a new treatment strategy."