Understanding the gastrointestinal nervous system

We have all suffered from stomach ache or bowel discomfort. These feelings, as well as more extensive gut pain, are regulated by signals between neurons in the gastrointestinal tract. Marcin Szczot wants to learn more about this part of the nervous system and various classes of sensory neurons that give rise to those feelings.

Marcin Szczot

PhD, Biophysics

Wallenberg Academy Fellow 2019

Linköping University

Research field:
The gastrointestinal nervous system

There are 100 million neurons in the gastrointestinal tract alone, and they are interlinked in different networks that have specific tasks. Szczot explains:

­“The nervous system in the gut and intestines is enormous, and in my view one of the most beautiful systems in the body. The gastrointestinal tract is a vital part of our biology.”

Szczot points out that most neuronal networks in the gastrointestinal tract do their work without our being aware of it. The enteric nervous system regulates how the intestines move and how quickly they work, while the sympathetic nervous system signals information about nutrition and contents to the brain.

“However, we also have a neuronal network that is responsible for the sensory feelings we experience consciously from the gut and intestines, such as bloating and pain. It gives us feedback about the status of our intestines via so called primary sensory neurons, which send signals to the central nervous system in the spinal cord. This is the system I’m mainly interested in.”

In inflammatory bowel disease IBD, and irritable bowel syndrome, IBS, this system becomes hyperactive and trigger extensive and persistent pain in the lower gastrointestinal tract.

“Although my research concerns fundamental physiological mechanisms, I’ll also be addressing some of the problems that can arise as a result of this hyperstimulation of the pain system. For instance, does the activity of certain neuronal types change when you have IBD or IBS? If we understand how primary sensory neurons drive hypersensitivity, we might be better able to deal with the problem itself.”

Experience from different fields

Szczot moved to Sweden and Linköping University in fall 2020 to set up his own research team. Before then he had been researching mechanical stimulation of the skin at the National Institutes of Health in the U.S. He is originally from Opole in western Poland, where he received his PhD in biophysics at Wroclaw Medical University.

“I trained first as an electronic engineer. But when I studied electronic circuits, I realized that many problems related to information processing had already been solved by nature and evolution in a much more exciting and intricate way than anything we humans can create. Therefore, I also took a degree in biology, and turned my attention to biophysics. Many of the problems arising in electronics, such as signal processing, I also meet in physiology and neuroscience. So, my experience from different scientific fields has been really useful.”

The emphasis of the research was first molecules and then cells. Szczot has recently shifted the focus of his work to even higher levels of biological organization. He is studying groups of cells, how they react and are activated together, and how they create a perception of the world outside the gastrointestinal tract. It is known that there are many groups of primary sensory neurons with different functions and molecular traits. Szczot elaborates:

“Take the skin, for example. It contains among other groups of neurons that signal only itching. We don’t have the same in-depth knowledge of functional specificity of neuronal classes in the intestines. Part of my project as a Wallenberg Academy Fellow is to study how signaling from groups of primary sensory neurons affects processes in the central nervous system, found in the brain and spinal cord, and how they create different sensations.”

“It gives me scientific freedom – a fantastic feeling. I can be creative and ponder different problems, as well as form a team of like-minded researchers who can help me and actively contribute to the process.”

Powerful tools

In the laboratory Szczot’s research team is examining neuronal activity in mice. To see what happens, they first need to manipulate the nervous system.

“One of our methods is classical physiology, where we use numerous sensory stimuli to activate neurons inside and outside the colon. The other, more modern, method is mouse genetics. This enables us to select a specific cell group, activate it in a specific place and time, and with a specific intensity.”

They use proteins that emit bright light when the cells are activated, which enables them to see under the microscope what is happening in the nervous system following manipulation in real time.

“The advantage of this method is that we can observe many neurons simultaneously and collect lots of data. We’ll be analyzing all the data in the hope of understanding the different patterns of activity that are triggered when the colon is stimulated.

Szczot enjoys the dynamic research environment at Linköping.

“As basic researcher, I delve deep into molecular and cellular mechanisms to understand processes, but however fascinating it is, I always wonder whether what we’re studying in animal models is relevant to human biology and medicine. Linköping has an impressive team of clinical scientists and I expect that close collaborations with clinically oriented groups will give me a unique perspective, and a chance to find answers to these questions.”

Text Susanne Rosén
Translation Maxwell Arding
 Johan NIlsson, Magnus Bergström, Marcus Marcetic, SciLifeLab