No spikes in this worm: Motor neurons without action potentials

If you know a little bit about neurons, even really basic stuff, you probably know that neurons send signals with action potentials (a.k.a. spikes). What fewer people know is that there is great diversity in how neurons signal. There are many sensory neurons and interneurons that work entirely without action potentials.

I once asked my Ph.D. supervisor, Dorothy Paul, “Is there such a thing as a non-spiking motor neuron?” Dorothy did most of her research working on non-spiking sensory neurons in the west coast mole crab, Emerita analoga. She didn’t give me the answer, but told me it was an excellent question and I should think about it. Some time later, I heard another student asking the same question to another researcher at a poster at a Society for Neuroscience poster, and the person said, “No.”

This paper says the answer is, “Yes.” There are non-spiking motor neurons.

Qiang Liu and colleagues did their research on the little nematode worm, Caenorhabditis elegans, and were able to take advantage of the huge knowledge of the genetics of this beast, and our ability to manipulate this animal’s genes. They recorded the output of muscle cells using standard electrical recordings, but instead of using electricity to stimulate the motor neurons controlling those muscles – the classical way of doing things – they genetically engineered the worm.

The authors were able to make the worms express a protein called channelrhodopsin in certain neurons. Rhodopsin is a visual pigment that responds to light. When you flash a light on these worms (did I mention they’re transparent?), the channelrhodopsin opens up a channel that allows electrical current to flow into the neuron. Thus, you can use a flash of light to fire neurons of your choosing.

In neurons with action potentials, activity is like a light switch: flipping the switch harder doesn’t make the light from the bulb any brighter. A key set of data is to increase the light intensity stimulating the motor neurons (shown by different line colours in the figure here), and record the response of the motor neurons. If there was a classic action potential in the motor neuron, you’d expect there to be no response until you hit a threshold, and always the same response in the muscle. But the effect is more like a dimmer than a switch: the greater the light intensity to the motor neurons, the more the muscles responded. This is just what you would as expect for a non-spiking neuron.

There rest of this paper revolves around characterizing the synaptic connections between motor neuron and muscle in much more detail. It mainly looks at how the strength of connections between the cells change with repeated stimulation of the motor neurons.

This is not the first demonstration of non-spiking motor neurons. Another nematode, Ascaris, probably claimed that honor two decades ago (Stretton and Davis 1989). So while I did learn quite a bit from this paper (I didn’t know about the Ascaris work) and am impressed with the techniques in this paper, I am still a bit puzzled as to why it’s in Proceedings of the National Academy of Science (PNAS). PNAS is one of those exclusive high profile journals, sometimes disparagingly called a “glamour mag,” that publishes on what it considers to be “high impact” science. I guess this paper made it in because C. elegans has become such an important model organism, because this paper doesn’t show any previously unknown or unexpected kind of phenomenon.

But considering that the Ascaris work was published before I asked my supervisor about non-spiking motor neurons, I suppose that the phenomenon could stand to be much better known in the neurobiology community.

References

Liu Q, Hollopeter G, Jorgensen E. 2009. Graded synaptic transmission at the Caenorhabditis elegans neuromuscular junction Proceedings of the National Academy of Sciences 106(26): 10823-10828. DOI: 10.1073/pnas.0903570106

Davis RE, Stretton AO. 1989. Signaling properties of Ascaris motorneurons: graded active responses, graded synaptic transmission, and tonic transmitter release. J Neurosci 9(2):415-425. http://www.jneurosci.org/cgi/content/abstract/9/2/415