Proprioceptive Sensory Neuron Subtype Genes Identified

We’re all familiar with the five senses that allow us to experience our surroundings: sight, hearing, smell, taste, and touch. Proprioception, or the sixth sense, is equally important but much less well-known.

Proprioception is what allows the central nervous system to send the correct signals to muscles via motor neurons, allowing us to perform a specific movement.

“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,”

Dr. Niccolò Zampieri, of the Max Delbrück Center in Berlin, said.

Zampieri and his team have written a paper about the molecular markers of the cells that are involved in this sixth sense. Researchers should be able to learn more about how proprioceptive sensory neurons (pSN) work because of what they found.

Proprioception Sensory Neurons

This sixth sense, which is not conscious like the other five, is what keeps us from falling over in the dark and lets us lift a cup of coffee to our mouths in the morning with our eyes closed.

That’s not all, though. People who don’t have proprioception can’t move in a coordinated way.

The cell bodies of proprioceptive sensory neurons are found in the spinal cord’s dorsal root ganglia. They are linked to the muscle spindles and Golgi tendon organs, which constantly register stretch and tension in every muscle in the body, via long nerve fibers.

This information is sent by the pSN to the central nervous system, where it is used to control motor neuron activity so that we can move.

“One prerequisite for this is that pSN precisely connect to different muscles in our bodies,”

said lead author Dr. Stephan Dietrich, a member of Zampieri’s lab.

Distinguishing Molecular Markers

However, little was known about the molecular programs that allow for these precise connections and give the muscle-specific pSN its distinct identity. As a result, the researchers used their study to look for molecular markers that distinguish the pSN for the abdominal, back, and limb muscles in mice.

The researchers used single-cell sequencing to determine which genes in the pSN of the abdominal, back, and leg muscles are read and translated into RNA.

“And we did find characteristic genes for the pSN connected to each muscle group. We also showed that these genes are already active at the embryonic stage and remain active for at least a while after birth,”

said Dietrich. This means that genetic programs determine whether a proprioceptor innervates the abdominal, back, or limb muscles.

Nascent Nerve Fiber Guidance

proprioception sensory neurons
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 Berlin researchers identified several genes for ephrins and their receptors among their findings.

“We know that these proteins are involved in guiding nascent nerve fibers to their target during development of the nervous system,”

said Dietrich. In mice unable to produce ephrin-A5, the connections between the proprioceptors and the muscles of the hind legs were found to be impaired.

The markers identified by the team should now aid in the investigation of the development and function of muscle-specific sensory networks.

“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,”

said Zampieri.

Improving Neuroprosthetics

Patients, such as those with spinal cord injuries, should eventually gain from this knowledge.

“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,”

said Zampieri.

He noted that Israeli researchers have recently discovered that healthy proprioception is essential for a healthy skeleton. For instance, scoliosis is a condition that can develop during childhood growth and causes the spine to become curved and twisted.

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

Zampieri added.

Hip dysplasia, an abnormality of the hip joint, may also be a result of defective proprioception. If science can gain a better understanding of our sixth sense, it may be possible to create novel therapies that effectively combat these and other forms of skeletal damage.

Reference: Dietrich, S., Company, C., Song, K. et al. Molecular identity of proprioceptor subtypes innervating different muscle groups in mice. Nat Commun 13, 6867 (2022).

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