Genetic alterations make the neurons in this rat's gut glow green when they fire. This video shows one of the first views of the enteric nervous system in action. [Xileng Shen/Duke University]


Scientists at Duke University report that they have developed a system that allows real-time optical and electrical observations of the gut's nervous system in a live animal. They note that such a view of the enteric nervous system will provide a new way to study gastrointestinal disorders

Consisting of five times more neurons than the spinal cord and often termed as a “second brain,” the enteric nervous system is a mesh-like sheath of neurons that controls the gastrointestinal tract. It regulates how food moves through the digestive system and communicates potential problems to the immune system. And while it has a direct line to both the brain and spinal cord, the enteric system has the ability to direct the organs under its control independently of either system.

Despite its importance, however, little is known about the enteric nervous system, such as how it responds to medications or what can go wrong with it to cause disease.

“About one-quarter of the world's population is affected by a functional gastrointestinal disorder,” said Xiling Shen, Ph.D., associate professor of biomedical engineering at Duke and author of the study (“Simultaneous Optical and Electrical In Vivo Analysis of the Enteric Nervous System”), which appears in Nature Communications.

Dr. Shen and his team implanted a transparent window made of borosilicate glass into the skin over the stomachs of mice. With no skull or bone structures to anchor the window, he needed to devise a 3D-printed surgical insert for stabilization. The device prevents the intestines from moving too much while maintaining normal digestive functions, allowing researchers to look at the same spot over multiple days. Dr. Shen also devised a system to record both electrical and optical activity at the same time.

The experiment uses transgenic mice with nerves that light up with a green hue when firing. By using a transparent graphene sensor to obtain electrical signals from the nerves, Dr. Shen gained an unobstructed view of the neural activity.

The optical signal gives spatial resolution, allowing researchers to tell which neuron is firing. The electrical signal provides time resolution, which pins down the exact waveform of the firing neurons. Dr. Shen said the enteric nervous system is now ready to be explored.

“So much is known about the brain and spinal cord because we can open them up, look at them, record the neural activities and map their behaviors,” he continued. “Now we can start doing the same for the gut. We can see how it reacts to different drugs, neurotransmitters, or diseases. We have even artificially activated individual neurons in the gut with light, which nobody has ever done before. This innovation will help us understand this 'dark' nervous system that we currently have completely no idea about.”







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