Scientists finally uncovered how the sixth sense works

[June 9, 2023: Staff Writer, The Brighter Side of News]

In order to perform synchronized movements, our bodies depend on specific sensory neurons located in our muscles and joints. These neurons are crucial for the brain to be aware of the body's actions. A research group headed by Niccolò Zampieri has investigated the molecular markers of these neurons to gain deeper insight into their functioning and has published their findings in Nature Communications.

The five senses - vision, auditory, olfaction, gustation, and tactile perception - are well-known as the primary means by which we interact with and perceive our environment.

Of equal significance but not as widely recognized is the existence of a sixth sense. This sense is responsible for gathering data related to our movements, posture, and spatial positioning from our muscles and joints, and then transmitting this information to our central nervous system. Dr. Niccolò Zampieri, who leads the Development and Function of Neural Circuits Lab at the Max Delbrück Center in Berlin, explains this crucial function.

“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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This intuitive perception, completely distinct from the other five senses and entirely subconscious, is what prevents us from toppling over in darkness and enables us to lift a cup of coffee to our lips with closed eyes in the morning. However, that's not the extent of its significance: "Individuals lacking proprioception are unable to execute coordinated movements," explains Zampieri.

Zampieri and his colleagues have recently published a paper detailing the molecular indicators of the cells engaged in this intuitive perception. These discoveries are expected to assist scientists in gaining a deeper comprehension of the functioning of proprioceptive sensory neurons (pSN).

The cell bodies of the pSN are situated in the spinal cord's dorsal root ganglia. These cells are linked through extensive nerve fibers to muscle spindles and Golgi tendon organs, which continually monitor stretch and tension within all the body's muscles. The pSN transmits this data to the central nervous system, where it governs motor neuron activity, enabling us to execute various movements.

According to Dr. Stephan Dietrich, a member of Zampieri’s lab, “One prerequisite for this is that pSN precisely connect to different muscles in our bodies.” On the other hand, very little information was available about the molecular processes that facilitate these accurate connections and give the muscle-specific pSN their distinct characteristics.

“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.

Through single-cell sequencing, the researchers analyzed the genes in the pSN related to the abdominal, back, and leg muscles, determining which ones are transcribed into RNA. Dietrich notes that they discovered specific genes associated with each muscle group's pSN. Moreover, they demonstrated that these genes are active during embryonic development and continue to be active for some time after birth. According to Dietrich, this suggests that predetermined genetic programs dictate whether a proprioceptor will connect with the abdominal, back, or limb muscles.

The Berlin-based scientists also identified multiple genes related to ephrins and their receptors in their findings. Dietrich explains that these proteins are known to play a role in directing developing nerve fibers toward their intended targets during nervous system development. The researchers observed that, in mice lacking the ability to produce ephrin-A5, the connections between proprioceptors and hind leg muscles were compromised.

“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.

In time, this knowledge should 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.

Moreover, he mentions that scientists in Israel have recently found that well-functioning proprioception is crucial for maintaining a robust skeletal structure. Scoliosis, a condition that occasionally emerges during growth in childhood, leads to a distorted and contorted spine.

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

Hip dysplasia, a malformation of the hip joint, could potentially be linked to improper proprioception. This possibility has inspired Zampieri to contemplate additional implications 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.”

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