Summary: Alcohol use disorder ( AUD) disrupts cognitive flexibility, crucial for learning and adapting to change. Recent research has discovered that alcohol-related chronic exposure alters the firing patterns of cholinergic interneurons ( CINs ), important striatal neurons that control dopamine and affect reward-driven learning.
Generally, CINs fire in a burst-pause style essential for unlearning ancient behaviors and adopting new ones, but drinking coverage shortens and weakens these pauses, impairing adaptability. The findings show potential therapeutic targets for treating neurological conditions and mental impairments caused by AUD.
Important Information:
- CIN Disruption: Chronic alcohol usage affects CIN burst-pause fire, essential for inversion understanding.
- Acetylcholine’s Role: CINs control choline, affecting resilience and overcoming obsolete manners.
- Results suggest CIN-targeted therapies may be able to treat AUD cognitive deficits.
Origin: Texas A&, M
Alcohol use disorder ( AUD) affects about , 400 million people , worldwide and is a leading reason of , major illnesses , such as cancer, cardiovascular disease, heart disease and stroke.
Beyond these natural impacts, AUD deeply disrupts mind functions essential for learning, memory and adaptability—key elements of mental versatility.
Now, researchers at the , Texas A&, M University College of Medicine , have shed new light on how severe alcohol use alters head signaling pathways, particularly focusing on how it impairs mental flexibility.  ,
Their findings, recently published in , Science Advances,  , demonstrate , the significant role of cholinergic interneurons ( CINs ) in this process.
Zhenbo Huang, PhD, an interact research scientist in the laboratory of , Jun Wang, MD, PhD, and coworkers have demonstrated that alcohol disrupts the brain’s ability to adapt by altering the burst-pause firing habits of CINs—specialized cells that launch glutamate, a crucial hormone.
CINs are critical gatekeepers in the brain’s striatum, influencing reward-driven learning and motivation by modulating dopamine signaling.
” Dopamine neurons drive the brain’s reward system, while CINs act as the gatekeepers, filtering stimuli that activate these neurons”, said Wang, an associate professor at the Texas A&, M College of Medicine.
The researchers found that animal models of chronic alcohol exposure that were stimulated by CINs produced an altered firing pattern in comparison to those that were not exposed to chronic alcohol exposure using advanced tools like optogenetics, which uses light to control cells.
Normally, CINs 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.
” Reversal learning is a cornerstone of cognitive flexibility”, Wang explained. It makes it possible for people to “unlearn behaviors when rules or circumstances change,” a process that heavily relies on acetylcholine signaling.
The team discovered that different roles for different CIN firing phases by combining optogenetics, which uses light to regulate CIN activity, and fiber photometry, which uses genetically engineered biosensors to detect real-time release of acetylcholine while subjects perform tasks.
The “burst” phase, which increases acetylcholine release from CINs, aids extinction learning—where old behaviors are unlearned.
The “pause” phase,  , on the other hand, which causes a dip in acetylcholine release from the CINs, is crucial for reversal learning, where new behaviors replace outdated ones.
This ground-breaking study explores how alcohol impairs these mechanisms, giving fresh insights into the broader effects of AUD. Importantly, the findings point to potential therapeutic options for treating AUD-related cognitive impairments.
” The burst and pause dynamics of CINs are critical for behavioral adaptability”, Wang said.
This study “displays the foundation for investigating how similar mechanisms might influence conditions beyond addiction, including aging and neurodegenerative diseases,” and “it highlights their unique roles.”
The Wang team is working to translate their discoveries into cutting-edge treatments for a variety of brain disorders as they continue to investigate how CIN dynamics impact brain health.
Funding: Their research is funded by the National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) /NIH.
About this news about AUD and cognition research
Author: Darren Benson
Source: Texas A&M
Contact: Darren Benson – Texas A&M
Image: The image is credited to Neuroscience News
Original Research: Open access.
Zhenbo Huang and colleagues ‘” The striatal cholinergic interneurons ‘ dynamic responses affect behavioral flexibility..” Science Advances
Abstract
The striatal cholinergic interneurons ‘ dynamic responses affect behavioral flexibility.
Striatal cholinergic interneurons ( CINs ) are essential for controlling behavioral flexibility, requiring both the adoption of new behaviors and the extinguishment of previously learned ones. However, the mechanisms driving these processes remain elusive.
We first demonstrate in this study that chronic alcohol consumption impairs behavioral flexibility and disrupts the burst-pause dynamics of CINs.
Next, we sought to understand the mechanisms by which behavioral flexibility is influenced by CIN dynamics. We discovered that extinction learning promotes acetylcholine (ACh ) release and that optogenetic induction of CIN burst firing speeds up the extinction process.
Additionally, we demonstrate that the goal-directed behaviors’ updating can be reversed by preventing CIN pauses by continuously optogenetic stimulation.
Overall, we demonstrate that CIN burst firing, which increases ACh release, promotes extinction learning, aiding the extinguishment of learned behaviors. Conversely, CIN firing pauses, which lead to ACh dips, are crucial for reversal learning, facilitating the adaptation of new actions.
These findings provide some insight into how CIN dynamics affect behavioral flexibility.
