The classic saying, "When wine enters, wisdom departs," encapsulates the enduring wisdom regarding alcohol's negative effects on the brain. While its short-term impacts on judgement are widely understood, current study indicates that persistent alcohol use produces severe, long-term alterations to brain systems crucial for adaptability and learning.

A study conducted by researchers at Texas A&M University's College of Medicine and published in Science Advances sheds light on how alcohol use disorder (AUD) alters brain signalling pathways. The study shows that AUD changes the way cholinergic interneurons (CINs) fire in the striatum of the brain, which makes it harder to think of new ideas.

Cognitive flexibility—the ability to unlearn old behaviours and adapt to new situations—is critical for survival and learning. The study focusses on how CINs, specialised neurones that regulate the neurotransmitter acetylcholine, play an important part in this process.

"Dopamine neurones drive the brain's reward system, while CINs act as gatekeepers, filtering stimuli that activate these neurones," says Jun Wang, MD, PhD, an associate professor at Texas A&M.

In healthy brains, CINs fire in a "burst-pause" pattern: bursts of activity produce acetylcholine, which promotes learning, while pauses allow the brain to unlearn old behaviours and adapt to new ones. However, in chronic alcohol-exposed mice, this precise pattern is altered, resulting in shorter and weaker pauses.

"Reversal learning is a cornerstone of cognitive flexibility," Wang says. "It allows individuals to unlearn behaviours when rules or circumstances change—a process heavily reliant on acetylcholine signalling."

The researchers investigated CIN (cholinergic interneuron) activity using advanced techniques like optogenetics, which enables light-based control of cells, and fibre photometry, which allows real-time detection of acetylcholine release. They identified distinct roles for the two phases of CIN firing: the "burst" phase facilitates extinction learning, helping the brain unlearn behaviors, while the "pause" phase supports reversal learning and the acquisition of new behaviors. Notably, alcohol exposure diminished both phases, impairing cognitive flexibility and adaptability.

"This study highlights their unique roles and lays the groundwork for exploring how similar mechanisms might influence conditions beyond addiction, including ageing and neurodegenerative diseases," according to Wang.

The findings highlight the broad consequences of alcohol on brain health. Beyond AUD, altered CIN firing patterns could help researchers understand ageing-related cognitive loss and neurodegenerative disorders such as Alzheimer's.

Importantly, the study highlights CIN-targeted therapies as a possible therapeutic option. Restoring burst-pause firing patterns may assist in reducing cognitive impairments associated with AUD and other neurological illnesses.

Alcohol consumption disorder affects roughly 400 million people globally, contributing to significant health issues, including cancer, liver disease, and stroke. Aside from physical suffering, its cognitive consequences—such as reduced learning and adaptability—are equally catastrophic.

Supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the Texas A&M research team continues to investigate how CIN dynamics affect brain health. Their research may lead to novel medicines, providing hope for those suffering with AUD and similar diseases.

While the proverb "When wine enters, wisdom departs" may have come from folklore, contemporary neuroscience verifies its timeless reality. Chronic alcohol consumption not only impairs judgement, but it also rewires the brain, reducing its capacity for development and change.