by Netherlands Institute for Neuroscience - KNAW

Graphical abstract. Credit: iScience (2024). DOI: 10.1016/j.isci.2024.111410

Neuroscientist Rogier Min from the Amsterdam UMC has collaborated with Christiaan Levelt's lab from the Netherlands Institute for Neuroscience and discovered how brain cells may react to cannabis, along with its potential impact on our brain's flexibility. The study is published in the journal iScience.

Cannabis binds to the so-called Cannabinoid receptor 1 (CB1 receptor), one of the most common receptors in our brain. CB1 receptors serve as switches that can turn various biological processes on or off. Under normal circumstances, the CB1 receptors are activated by cannabis-like substances that are produced in the brain. For a long time, CB1 receptors were believed to be situated only on nerve cells (neurons), but the team has shown that another player is involved as well: astrocytes.

Astrocytes are a type of glia cell in the brain and spinal cord. These cells play an important supportive role in the nervous system. The team discovered that the CB1 receptors located on these cells play an important role in how the brain develops, especially in one's earlier years.

The researchers specifically looked at a process known as plasticity—which is how the brain adjusts and changes. At younger ages, there are certain periods when the brain has heightened plasticity, meaning that it can adapt and change more easily. This is known as the critical period.

Levelt says, "In earlier studies from the 80s, researchers injected astrocytes from a kitten into the visual cortex of an older cat, the brain area involved in vision. As a result, the critical period was opened once more, meaning that the brain could adjust more easily again. We also know that the CB1 receptor in astrocytes is expressed less and less as we age. Could there be a link here? And could this mean that the CB1 receptor on astrocytes play a role in this critical period plasticity?"

To investigate this, the team used a special mouse model in which the CB1 receptors of specific cells were turned off: either only on the nerve cells, or only on the astrocytes. They examined whether the absence of the receptor influenced the development of the inhibitory system in the brain.

Our brain consists of both stimulating and inhibitory nerve cells. We need the inhibitory cells, also known as interneurons, to keep our brain activity balanced. This study focused on the visual cortex, the part of the brain that helps us process what we see.

The researchers discovered that removing the CB1 receptors from astrocytes meant that the brain could less easily adjust to changes during development. Min says, "We found this by temporarily covering the eye of a young mouse during the critical period for vision. In normal mice, their brain is capable of adapting to this by strengthening the connection to the 'good eye.'

"Mice without CB1 receptors on the interneurons seemed to follow a similar adaptability as the control mice. However, in the mice without CB1 receptors on the astrocytes, this adaptability didn't work effectively. These findings show that astrocytes in particular, and not nerve cells, play an important role in this process, which is surprising."

In addition to offering a better understanding of how the brain develops, the research can also help explain how cannabis use at a younger age can introduce some risks. Studies looking at the long-term effects of cannabis on the brain are not conclusive. But there are indicators that, if the CB1 receptor is disturbed during brain development, there may be problems with learning, memory, or other brain functions.

While young children usually don't use cannabis, teenagers and young adults are a particular risk group. Their brains are then still developing: especially the prefrontal cortex, the part that is involved in planning and decision-making.

Min says, "The CB1 receptor is involved in numerous processes in the brain. It's actually extraordinary that the binding of cannabis to the CB1 receptor doesn't typically result in big problems. Our research could explain some negative consequences of cannabis: the CB1 receptor on astrocytes appears to be an important player in early brain development, and disrupting this process can impact the amount that our brain can adjust.

"While cannabis is often seen as relatively safe, it can still influence brain development at younger ages. Now we have a slightly better impression of how and why that happens."

More information: Rogier Min et al, Inhibitory maturation and ocular dominance plasticity in mouse visual cortex require astrocyte CB1 receptors, iScience (2024). DOI: 10.1016/j.isci.2024.111410

Journal information: iScience 

Provided by Netherlands Institute for Neuroscience - KNAW