Proprioception allows people to know the position of parts of the body without seeing them, enabling us to touch type, walk in the dark without falling over, or drive a car while looking at the road. Defects in this sensory system cause uncoordinated movements—for example, trouble walking despite fully functional limbs. Few motor outputs in animals don’t involve some sort of proprioception, which is sometimes labeled a “sixth sense.” And yet we know very little about its underlying mechanisms.
Now, a team in South Korea has identified a group of sensorimotor neurons responsible for proprioception in the roundworm Caenorhabditis elegans. They also identified a previously unknown function for proprioceptive neurons: regulating and coordinating muscle movement. The research was published in PLOS Biology.
C. elegans normally propels itself forward or backward by undulating its body up and down in a sinusoidal wave pattern. But when the research team used lasers to burn out a pair of dorsal neurons, called SMDD-Left and SMDD-Right, which stimulate contractions of the head and neck muscles, the worms spun in a perpetual somersault, a contrast with their normal movement. Similarly, burning out the SMD neurons on the ventral side (called SMDV for ventral) resulted in a perpetual backflip.
These observations—and additional experiments in which optogenetic activation of SMD neurons stimulated head steering, and calcium imaging revealed SMD activation during neck bending—confirmed the proprioceptive role of the SMD neurons in facilitating proper steering of the worm’s body via coordinated contractions of the head and neck muscles. “The shape and connectivity of the SMD neurons suggested that they might be proprioceptive, but nobody actually confirmed it until now,” says Gal Haspel, a neuroethologist at the New Jersey Institute of Technology who was not involved in the study.
Next, the team investigated the molecular mechanism behind the proprioceptive function of the SMD neurons. They found that only double mutants lacking two SMDD ion channels, called transient receptor potential cation (TRPC) channels TRP1 and TRP2, exhibited the abnormal circling behavior. Interestingly, SMDD activity did not stop altogether in the double mutants. Instead, head and neck muscle activation simply became misregulated. “If you take the sensory feedback away, the worm doesn’t stop moving, it just makes a mistake,” Haspel says.
Together, these observations suggest that the TRP ion channels not only act as sensors of body position but also provide feedback to the SMDD neurons, telling them when to signal head and neck muscles to contract in order to properly steer. Without the feedback, the worm’s neck bends too far for too long in one direction, sending the worm into a circular path.
“TRP1 and TRP2 are muscle stretch-sensitive channels that detect body movement,” explains lead author Jihye Yeon, a neuroscientist at the Daegu Gyeongbuk Institute of Science and Technology (DGIST) in South Korea. “Before, we didn’t know that these stretch receptors could also coordinate and regulate locomotion.”
Based on their findings, Yeon and colleagues suggest a model for the proprioceptive feedback loop involving the SMDD neurons which are mediated by the two sensory TRP ion channels. “It is hard to say which comes first, the bending or the sensing, but we demonstrated that TRP1 and TRP2 sense the bent head and coordinate the SMDD neuronal activity, which in turn regulates the head/neck muscle activity and results in the sinusoidal wave movement,” she says.
While the study provides abundant evidence that the two TRP ion channels are essential proprioreceptors regulating coordinated locomotion in C. elegans, Yeon says that several questions remain. First, she would like to electrophysiologically confirm role of TRP1 and TRP2 in sensing muscle stretch. And although the two TRP ion channels are also expressed in the SMDV pair of neurons, it is unclear why they function normally in TRP double mutants and what other proprioreceptive molecules may be responsible.
TRP ion channels serve a variety of functions that are evolutionarily conserved among species. Yeon is therefore confident that studying simple locomotion in the worm will one day lead to a better understanding of proprioception in humans.