Throughout the animal kingdom, there are numerous examples of neurons that respond to multiple stimuli and faithfully transmit information about those various inputs. In the mouse, for example, there are certain neurons that respond to both temperature and potentially damaging touch. In the fruit fly, there are neurons that sense light, temperature, pain, and proprioceptive stimuli—those arising as a result of body position and movement. And in C. elegans, two sensory neurons, known as PVD neurons, that run the length of the body on either side are thought to regulate proprioception as well as responses to harsh touch and cold temperature.
Scientists have now figured out how a single PVD neuron can relay two different stimuli: while harsh touch results in typical firing of the neuron—an impulse that travels the length of the cell—proprioception causes a localized response in one part of the cell with no apparent involvement of the rest. The findings are reported today (November 14) in Developmental Cell.
“[The] paper illustrates that different parts of the neuron do different things,” says neuroscientist Scott Emmons of Albert Einstein College of Medicine who did not participate in the research, “and that just makes the whole system much more complex to interpret,” he says.
To examine how a single neuron interprets distinct inputs and drives corresponding behaviors, neuroscientist Kang Shen of Stanford University and colleagues focused on PVD neuron–regulated escape behavior when a worm is poked with a wire and the worm’s normal wiggling motion as it responds to proprioceptive stimuli.
Mechanosensory protein channels in the neuron’s membrane are the starting point for the cell’s response to a stimulus, so the team analyzed worms with mutations in a variety of such PVD-produced proteins to see if distinct channels were responsible for the different stimuli. This led to the discovery that the channels DEL-1, UNC-8, and MEC-10 were necessary for normal wiggling but not for escape, while the channel DEGT-1 was needed for escape but not wiggling.
But, figuring out the specific channels involved is only half the puzzle, Shen explains. It remained unclear how the cell processed the inputs downstream of these channels. PVD neurons have vast branching dendrites through which the various mechanosensory stimuli are received, but only one axon that then delivers this information to one downstream target cell. “We worked really hard to understand how a single axon can encode both of these stimuli,” Shen says “and we really couldn’t explain what was happening.”
It turned out that the different stimuli acting on the distinct channels caused particular calcium responses inside the cell. “If you bang the worms with [the] wire you see this sweeping calcium increase throughout the dendritic arbor that then goes to the cell body,” as would be expected for typical neuronal signals, explains Shen. But, when the worm is simply moving normally, calcium signals in the cell body are distinctly lacking. “We had assumed that [the cell] needs to be firing at the frequency of the body undulations,” Shen says, but it turned out that while calcium signals in the dendrites occurred at a frequency in line with the wiggling motion, those in the cell body were rare. This indicated that the signals “do not propagate” beyond the dendrite, says Shen. “When we saw that [result], we were like, ‘aha!’”
The team went on to show that the worms’ normal wiggling motion remained intact even when the function of the PVD neuron’s synapse (the terminus of the axon that connects with the downstream cell) was perturbed. By contrast, such tampering prevented escape behavior. They also showed that while wiggling did not prompt whole-cell firing, it did cause localized dendritic release of a neuropeptide called NLP-12, and this was critical for normal wiggling but not escape behavior.
“It looks like, [for one of the stimuli], the dendrite itself, without utilizing the cell body and the axon can communicate with other cells. . . . That to me makes it really interesting because it suggests there might be local events going on that we hadn’t considered previously,” says molecular neurobiologist Sreekanth Chalasani of the Salk Institute who was not involved in the research. “It’s very novel.”
Indeed, the results indicate that when using tools such as optogenetics that cause neurons to fire an action potential down the course of the entire cell, for example, “you may not fully unveil what the cell is doing,” says Shen, because “you are only investigating a certain aspect of its activity.”
We think of neural networks as “wiring diagrams,” adds Emmons, and “with an electrical wire you put an impulse on one side and it travels along to the other.” But this research shows that “neurons are simply not like that,” he says. “They are not wires at all. They are very complicated little computers.”
L. Tao et al., “Parallel processing of two mechanosensory modalities by a single neuron in C. elegans,” Dev. Cell, doi: 10.1016/j.devcel.2019.10.008, 2019.
Ruth Williams is a freelance journalist based in Connecticut. Email her at firstname.lastname@example.org or find her on Twitter @rooph.