Neuroscientists discovered how brain cells may react to cannabis, along with its potential impact on our brain’s flexibility.
New findings highlight the importance of the CB1 receptor on astrocytes in brain development and plasticity. Disrupting these receptors, as seen in studies with mice, hampers the brain’s adaptability during critical growth phases, potentially explaining some negative effects of early cannabis exposure on learning and memory, especially in adolescents and young adults.
Cannabinoid Receptors and Brain Function
Cannabis binds to a receptor called Cannabinoid Receptor 1 (CB1), one of the most abundant receptors in the brain. These CB1 receptors act like switches, controlling various biological processes by turning them on or off. Typically, they are activated by natural, cannabis-like substances produced within the brain. For years, scientists believed CB1 receptors were found only on nerve cells (neurons). However, recent research has revealed that another key player is involved: astrocytes.
The Role of Astrocytes in Brain Development
Astrocytes are a type of glial cell found in the brain and spinal cord that provide crucial support to the nervous system. Researchers have discovered that CB1 receptors on astrocytes play a significant role in brain development, particularly during early life. They focused on a phenomenon known as plasticity, the brain’s ability to adapt and change. During childhood and adolescence, there are specific windows of heightened plasticity, when the brain can adapt and reorganize more easily. These are called critical periods.
Investigating Astrocyte Influence on Brain Plasticity
Christiaan Levelt is a Professor of Molecular and Cellular Mechanisms of Cortical Development and Plasticity at the Faculty of Earth and Life Sciences (FALW) of VU Amsterdam. He explains that “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 plays 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.
Findings: CB1 Receptors and Brain Adaptability
The researchers discovered that removing the CB1 receptors from astrocytes meant that the brain could less easily adjust to changes during development.
Dr. Rogier Min is a Visiting Fellow, Integrative Neurophysiology Assistant Professor, Pediatrics at Amsterdam UMC. He explains, “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.”
Implications of CB1 Receptor Research on Neurodevelopment
This research helps us better understand how the brain develops. It can also help us 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 continues: “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 impressions of how and why that happens.”
Reference: “Inhibitory maturation and ocular dominance plasticity in mouse visual cortex require astrocyte CB1 receptors” by Rogier Min, Yi Qin, Sven Kerst, M. Hadi Saiepour, Mariska van Lier and Christiaan N. Levelt, 15 November 2024, iScience.
DOI: 10.1016/j.isci.2024.111410
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