Proprioception Sixth Sense Genes: New Hope for Movement Disorders
Author: Max Delbrück Center for Molecular Medicine in the Helmholtz Association
Published: 2022/12/09 - Updated: 2025/11/27
Publication Details: Peer-Reviewed, Research, Study, Analysis
Category Topic: Medical - Related Publications
Page Content: Synopsis - Introduction - Main - Insights, Updates
Synopsis: This research, published in the peer-reviewed journal Nature Communications, explores proprioception - often called our sixth sense - which allows the brain to track body position, movement, and spatial orientation without conscious effort. Scientists at the Max Delbrück Center in Berlin identified specific molecular markers in proprioceptive sensory neurons that connect to different muscle groups in the abdominal, back, and limb regions, discovering that these genetic programs are active from embryonic development through early life. The findings reveal how these specialized neurons, located in the spinal cord's dorsal root ganglia, create precise connections with muscle spindles and tendon organs to continuously monitor stretch and tension throughout the body.
This work has significant implications for people with spinal cord injuries, developmental conditions like scoliosis and hip dysplasia, and anyone who has lost coordination abilities, as understanding these cellular mechanisms could lead to improved neuroprosthetic devices that restore motor and sensory function. The research demonstrates that disrupted proprioception during childhood growth may cause skeletal abnormalities through altered muscle tension, opening pathways for preventive therapies. For older adults experiencing balance issues or individuals with neurological conditions affecting movement coordination, this fundamental research provides hope for targeted treatments that address the root cause rather than just managing symptoms - Disabled World (DW).
Defining Proprioception
- Proprioception
Proprioception, also called kinaesthesia or kinesthesia, is the sense of self-movement, force, and body position. It is sometimes described as the "sixth sense." The sense of proprioception is ubiquitous across mobile animals and is essential for the body's motor coordination. Proprioceptors can form reflex circuits with motor neurons to provide rapid feedback about body and limb position. These mechanosensory circuits are important for flexibly maintaining posture and balance, especially during locomotion. In humans, conscious proprioception is communicated by the dorsal column-medial lemniscus pathway to the cerebrum. Whereas non-conscious proprioception is communicated primarily via the dorsal spinocerebellar tract and ventral spinocerebellar tract to the cerebellum.
Introduction
To perform coordinated movements, we rely on special sensory neurons in our muscles and joints. Without them, the brain wouldn't know what the rest of our body was doing. A team led by Niccolò Zampieri has studied their molecular markers to better understand how they work and describes the results in Nature Communications.
Main Content
Sight, Hearing, Smell, Taste, Touch
We're all familiar with the five senses that allow us to experience our surroundings. 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."
This sixth sense - which, unlike the other five, is entirely unconscious - is what stops us from falling over in the dark, and what allows us to raise a cup of coffee to our mouth with our eyes shut in the morning. But that's not all:
"People without proprioception can't actually perform coordinated movements," says Zampieri.
He and his team have now published an article in the journal Nature Communications, in which they describe the molecular markers of the cells involved in this sixth sense. The findings should help researchers to better understand how proprioceptive sensory neurons (pSN) work.
Precise Connections Crucial
The pSN cell bodies are located in the dorsal root ganglia of the spinal cord. They are connected via long nerve fibers to the muscle spindles and Golgi tendon organs that constantly register stretch and tension in every muscle of the body. The pSN send this information to the central nervous system, where it is used to control motor neuron activity so that we can perform 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. "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 single-cell sequencing, the team investigated 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," says Dietrich. "We also showed that these genes are already active at the embryonic stage and remain active for at least a while after birth."
Dietrich explains that this means there are fixed genetic programs that decide whether a proprioceptor will innervate the abdominal, back or limb muscles.
Among their findings, the Berlin researchers identified several genes for ephrins and their receptors.
"We know that these proteins are involved in guiding nascent nerve fibers to their target during development of the nervous system," says Dietrich.
The team found that the connections between the proprioceptors and the rear leg muscles were impaired in mice that can't produce ephrin-A5.
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.
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 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.
"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."
Insights, Analysis, and Developments
Editorial Note: What makes this research particularly valuable is its dual focus on both basic science and practical application - the team didn't just map which genes control our body awareness, but traced how these molecular programs unfold from before birth and explained why their disruption leads to real-world problems like twisted spines and unstable joints. The beauty of studying proprioception lies in recognizing that this unconscious sense underpins nearly every physical action we take, from walking without watching our feet to maintaining balance when reaching overhead, yet most people remain unaware of its existence until it fails. By identifying the specific genetic switches that determine whether a sensory neuron will monitor an arm muscle versus a leg muscle, researchers have essentially created a wiring diagram for one of the body's most essential but overlooked systems, bringing us closer to the day when damaged neural circuits can be repaired or replaced with precision rather than hope - Disabled World (DW).Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Max Delbrück Center for Molecular Medicine in the Helmholtz Association and published on 2022/12/09, this content may have been edited for style, clarity, or brevity.