Study Shows How Alcohol Alters Brain Signaling, Impairing Cognitive Flexibility and Learning - Video

Researchers at the Texas A&M University College of Medicine have shed new light on how chronic alcohol use alters brain signaling pathways, specifically focusing on how it impairs cognitive flexibility. Their findings, recently published in Science Advances, demonstrate the significant role of cholinergic interneurons (CINs) in this process.

Researchers demonstrated that alcohol disrupts the brain’s ability to adapt by altering the burst-pause firing patterns of cholinergic interneurons —specialized neurons that release acetylcholine, a key neurotransmitter. cholinergic interneurons are critical gatekeepers in the brain’s striatum, influencing reward-driven learning and motivation by modulating dopamine signaling.

Using advanced tools such as optogenetics, which uses light to control cells, the researchers uncovered that stimulating cholinergic interneurons in animal models of chronic alcohol exposure produced an altered firing pattern compared to models without chronic alcohol exposure. Normally, cholinergic interneurons fire in a “burst-pause” pattern: a quick burst of activity followed by a pause, which is essential for learning new behaviors and adapting to change. However, in alcohol-exposed models, this firing pattern was significantly disrupted, with shorter and weaker pauses, impairing critical learning process such as reversal leaning.

By combining optogenetics—which uses light to control cholinergic interneurons activity—and fiber photometry—which involves genetically engineered biosensors to detect real-time release of acetylcholine while subjects perform tasks—the team discovered distinct roles for different cholinergic interneurons firing phases. The “burst” phase, which increases acetylcholine release from cholinergic interneurons, aids extinction learning—where old behaviors are unlearned. The “pause” phase, on the other hand, which causes a dip in acetylcholine release from the cholinergic interneurons is crucial for reversal learning, where new behaviors replace outdated ones.

Reference: Zhenbo Huang et al., Dynamic responses of striatal cholinergic interneurons control behavioral flexibility.Sci. Adv.10,eadn2446(2024).DOI:10.1126/sciadv.adn2446