As the holiday season rolls in, many of us are celebrating with family, friends, and – let’s be honest – a few extra glasses of eggnog. But while we indulge in festive cheer, it’s a good time to think about how alcohol affects not just our bodies but our brains too.
Researchers at Texas A&M University have made some discoveries about how chronic alcohol use impairs the brain’s ability to learn and adapt, particularly neurons called cholinergic interneurons (CINs). These are crucial in controlling dopamine signaling, which influences learning and motivation.
Alcohol can affect the body in many ways, both in the short-term (e.g. memory, balance, inhibitions), but also in the long-term, such as the development of Alcohol Use Disorder (AUD).
AUD is a global concern that affects 400 million people around the world and it can cause serious health issues like stroke, cancer, liver disease, and cardiovascular disease. It is also known to disrupt cognitive functions like cognitive flexibility, which involves adapting to new situations, memory, and learning.
Normally, CINs fire in something called a “burst-pause” pattern. As the name suggests, this is a quick burst of activity followed by a pause. We need this pattern for adapting and learning to new behaviors.
When the researchers looked at alcohol-exposed animal models, they found that the firing pattern had pauses that were weaker and shorter. This disrupted firing pattern meant that vital processes like reversal learning were impaired.
“Reversal learning is a cornerstone of cognitive flexibility,” Jun Wang, associate professor at the Texas A&M College of Medicine, explained in a statement. “It allows individuals to unlearn behaviors when rules or circumstances change – a process heavily reliant on acetylcholine signaling.”
The scientists in this group used a technique called optogenetics, which mixes optics and genetics to manipulate specific neurons. In this study, light was used to control cell activity, and genetically engineered biosensors were employed to detect acetylcholine release in real time while subjects performed tasks. This allowed scientists to see how changes in CIN firing can go on to affect learning.
It was discovered that the burst phase helped with unlearning old behaviors (a.k.a. extinction learning) and the pause phase was needed for learning new behaviors (reversal learning).
“The burst and pause dynamics of CINs are critical for behavioral adaptability,” Wang said. “This study highlights their unique roles and lays the groundwork for exploring how similar mechanisms might influence conditions beyond addiction, including aging and neurodegenerative diseases.”
Along with explaining how cognitive flexibility can be affected by alcohol, the information learned points towards potential therapeutic targets for treating AUD and other brain conditions caused by cognitive impairments.
These findings suggest that targeting the burst-pause firing pattern of CINs could lead to treatments that improve cognitive flexibility in some conditions.
This research is published in Science Advances.
