A new study from Texas A&M University reveals how chronic alcohol consumption impairs cognitive flexibility by altering the brain’s cholinergic interneurons. Discover the scientific insights and potential therapeutic targets unveiled by this pivotal research.
A new study by Texas A&M University has unveiled intricate mechanisms illustrating how chronic alcohol use disrupts crucial brain functions. The research, published in Science Advances, delves into the role of cholinergic interneurons (CINs) and how their activity is altered by alcohol, profoundly impacting cognitive flexibility.
Alcohol use disorder (AUD) is a global health crisis, affecting around 400 million individuals and contributing to severe conditions such as cancer, cardiovascular disease, liver disease and stroke. Beyond these physical consequences, AUD significantly impairs brain functions like learning, memory and adaptability — core components of cognitive flexibility.
Researchers at Texas A&M University College of Medicine, led by Zhenbo Huang, an associate research scientist in the laboratory of Jun Wang, have illuminated a critical aspect of this disorder.
Their findings reveal that chronic alcohol consumption disturbs the brain’s ability to adapt by altering the burst-pause firing patterns of specialized neurons called CINs, which release acetylcholine, a vital neurotransmitter.
“Dopamine neurons drive the brain’s reward system, while CINs act as the gatekeepers, filtering stimuli that activate these neurons,” Wang, an associate professor at Texas A&M College of Medicine, said in a news release.
The study utilized advanced methodologies such as optogenetics to manipulate CIN activity and fiber photometry to observe acetylcholine release in real time. These approaches allowed the researchers to explore the distinct functions of different CIN firing phases.
They discovered that the “burst” phase aids in extinction learning, the process of unlearning old behaviors, while the “pause” phase is crucial for reversal learning, which involves adopting new behaviors.
“Reversal learning is a cornerstone of cognitive flexibility,” Wang added. “It allows individuals to unlearn behaviors when rules or circumstances change — a process heavily reliant on acetylcholine signaling.”
Chronic alcohol exposure in animal models disrupted the normal burst-pause pattern of CINs, resulting in shorter and weaker pauses. This alteration impaired critical learning processes such as reversal learning, emphasizing the profound impact of alcohol on cognitive functions.
“The burst and pause dynamics of CINs are critical for behavioral adaptability,” Wang added. “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.”
The findings not only expand our understanding of the neural underpinnings of AUD but also suggest potential therapeutic targets for addressing cognitive impairments associated with alcohol use.
As the Wang team continues to explore the impact of CIN dynamics on brain health, there is hope for translating these discoveries into innovative treatments for various brain disorders, potentially offering relief for millions affected by addiction and other cognitive impairments.