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Scientists solve the mystery of how the sixth sense really works

Sight, hearing, smell, taste, touch: We’re all familiar with the five senses that allow us to experience our surroundings. (CREDIT: Creative Commons)

To move smoothly, we need special nerve cells in our muscles and joints. These cells help our brain understand what our body is doing. Niccolò Zampieri and his team looked at these nerve cells to learn more about them.

We all know about our five senses: seeing, hearing, smelling, tasting, and touching. They help us understand the world around us.


Equally important but much less well known is the sixth sense: “Its job is to collect information from the muscles and joints about our movements, our posture and our position in space, and then pass that on to our central nervous system”, says Dr. Niccolò Zampieri, head of the Development and Function of Neural Circuits Lab at the Max Delbrück Center in Berlin.

“This sense, known as proprioception, is what allows the central nervous system to send the right signals through motor neurons to muscles so that we can perform a specific movement.”


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Imagine you have a secret sense that you're not even aware of. Unlike your regular five senses like sight and hearing, this sixth sense works silently in the background. It's like a guardian angel that keeps you from tripping in the dark and helps you do things like sipping your morning coffee with your eyes closed. But there's more to it than just that. According to Zampieri, without this sense, people would struggle to do simple tasks smoothly.

Zampieri and his team recently wrote a paper for the journal "Nature Communications." In it, they talk about the tiny markers in our cells that are involved in this hidden sense. By understanding these markers, scientists hope to learn more about how our bodies can sense where they are in space and move accordingly.


Precise connections are crucial

The pSN cell bodies are found in a part of the spinal cord called the dorsal root ganglia. These cells are linked to muscle spindles and Golgi tendon organs by long nerve fibers. These organs are like sensors that detect how much our muscles are stretched or tensed up.

Different populations of sensory neurons cell bodies in a dorsal root ganglion (right) and their axons in the spinal cord (left): The cells in green detect proprioceptive information while the cells in red thermal and tactile information. (CREDIT: Stephan Dietrich, Zampieri Lab, Max Delbrück Center)

The pSN cells pass along information to our brain and spinal cord, which then helps control how our muscles move. This makes it easier for us to do things like walk, run, or pick up objects without any jerky movements.


“One prerequisite for this is that pSN precisely connect to different muscles in our bodies,” says Dr. Stephan Dietrich, a member of Zampieri’s lab. However, almost nothing was known about the molecular programs that enable these precise connections and lend the muscle-specific pSN their unique identity.

Schematic illustrating central and peripheral connectivity of e15.5 proprioceptors at thoracic (left) and lumbar (right) spinal levels. (CREDIT: Nature Communications)

“That’s why we used our study to look for molecular markers that differentiate the pSN for the abdominal, back and limb muscles in mice,” says Dietrich, lead author of the study, which was carried out at the Max Delbrück Center.


Guidance for nascent nerve fibers

Using a special method called single-cell sequencing, the team looked at which genes in certain muscle groups were being used to make RNA in the nervous system. Dietrich, one of the researchers, explains, "We found specific genes in the nervous system that are connected to each group of muscles in the abdomen, back, and legs."

They also discovered that these genes are active even before birth and stay active for some time after birth. Dietrich says this shows that there are certain genetic plans that determine whether a type of nerve cell will connect to muscles in the abdomen, back, or limbs.

One interesting thing they found was certain genes related to ephrins and their receptors. Dietrich explains, "These proteins help guide nerve fibers to the right place during the development of the nervous system." They noticed that in mice that couldn't make a protein called ephrin-A5, the connections between the nerves and the muscles in the rear legs weren't working properly.


One aim is better neuroprostheses

“The markers we identified should now help us further investigate the development and function of individual muscle-specific sensory networks,” says Dietrich. “With optogenetics, for instance, we can use light to turn proprioceptors on and off, either individually or in groups. This will allow us to reveal their specific role in our sixth sense,” adds Zampieri.

Representative image of tdTomato+ afferents in a lumbar spinal cord section from p7 Trpv1Cre; PvFlp; Ai65 mice. MMC, median motor column; LMC, lateral motor column. Scale bar: 100 µm. (CREDIT: Nature Communications)

This knowledge should eventually benefit patients, such as those with spinal cord injuries. “Once we better understand the details of proprioception, we’ll be able to optimize the design of neuroprostheses, which take over motor or sensory abilities that have been impaired by an injury,” says Zampieri.


Altered muscle tension causes a crooked spine

He adds that researchers in Israel have recently discovered that properly functioning proprioception is also important for a healthy skeleton. Scoliosis, for instance, is a condition that sometimes develops during growth in childhood and causes the spine to become crooked and twisted.

Proprioceptors muscle-type identity emerges at early developmental stages. (CREDIT: Nature Communications)

“We suspect this is caused by dysfunctional proprioception, which alters the muscle tension in the back and distorts the spine,” says Zampieri.


Hip dysplasia, an abnormality of the hip joint, might also be caused by faulty proprioception. This has led Zampieri to envision another outcome of the research: “If we can better understand our sixth sense, it will be possible to develop novel therapies that effectively counteract these and other types of skeletal damage.”

For more science and technology stories check out our New Discoveries section at The Brighter Side of News.


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