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Research Snapshot: New Discovery Describes How Motor Cortex Influences Stress Responses In Brain Regions Involved In Drug And Alcohol Seeking Behavior | Vanderbilt News

Series of delipidated (“cleaned”) mouse brains imaged using light-sheet microscopy to reveal neural circuits marked by viral tracing strategies.

This can lead to a collaboration to find targets affecting the motor cortex and look at the activity in a new light. Research suggests that movement and exercise may become a prescription.

Building on recent job, researchers including Danny winder, director of the Vanderbilt Center for Addiction Research have developed a clear picture of how particular circuits in the brain may be involved in drug and alcohol seeking behavior. They derived a control network for the nucleus of the terminal striae bed, part of a larger brain region sometimes called the extended amygdala.

The researchers used light-sheet microscopy, a technique that allows rapid, three-dimensional imaging of the entire brain, to examine every part of the brain that connects to the BNST circuit. These studies were carried out in parallel with studies exploring the activity of this circuit. By exploring the activity of this circuit in conjunction with a brief stressor (restriction), rather than lengthy alcohol abstinence tests, they were able to accomplish in two and a half days what would otherwise have taken 15 years.

Thanks to this analysis, the researchers were able to trace the relationship between the inputs and the outputs to confirm the operation of the circuit. Surprisingly, the study found that the upper regions of the brain that control the BNST network are the motor and premotor cortices, which are involved in the execution and planning of movement.


The motor cortex in the brain plays a major role in virtually every movement we make and affects other aspects of our life in unexpected ways. For example, we cannot tickle ourselves because this part of our brain tells us that the skin is about to be touched, we have a smooth visual field because the motor cortex tells the occipital cortex that our eyes are moving and anticipates where we’re gonna watch next. Movement is the most important and fundamental principle of animal biology, and systems must work together to make this happen, Winder said.

Danny winder

“We are now starting to see how motor cortex inputs impact brain circuitry involved in a potential relapse in drug and alcohol seeking behavior,” said Winder, also Bixler-Johnson-Mayes professor of molecular physiology. and biophysics, pharmacology and psychiatry. “We suspect that there are several ways to regulate this process, both positive and negative. While exercise can have a positive impact on sobriety, other motor activities can coordinate with inputs from that region of the brain that have a negative effect.

The research also emphasizes the impact of advanced neuroscientific tools on the field over the past decade. The light-sheet microscope allowed us to stop looking “under the lamppost,” Winder said. “Using a higher throughput, unbiased approach, we have opened up a new area of ​​neurobiology: the connection of the motor cortex with affective circuits. “


Winder hopes to delve into this work to understand and describe how this affective circuit works to describe phenomena such as “runner’s drunkenness”.

Ultimately, this early work could lead to a collaboration with experts in genomics and proteomics to seek new targets on entry affecting the motor cortex, to think about activity in a new light. Research suggests that movement and exercise may become a prescription.


This research supported by the National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of General Medical Sciences of the National Institutes of Health. Additional funding was provided by the Brain and Behavior Research Foundation.


The article, Delimitation of an insula-BNST circuit initiated by a control behavior that regulates avoidance in mice, was published in the journal Nature Communication June 11.

Collaboration within VCAR, itself a cross-institutional program, included work from laboratories specializing in behavior and physiology, neuroanatomy, molecular physiology and biophysics. The seam between the laboratories was made possible thanks to the efforts of the trainees Joe luchsinger and Samuel Centanni.

Other co-authors and contributors to the study are Jose maldonado and Richard B. Simerly, research instructor and professor of molecular physiology and biophysics, respectively and interns of the Winder laboratory Tracy fetterly, Greg Salimando, Marie doyle. Kellie M. Williford, ONS Outreach Coordinator for Vanderbilt Brain Research also participated in the work.


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