When Lidia Szczupak found herself in a scientific rut, she turned to the medicinal leech Hirudo verbana to help her wriggle out of it.
She had been studying how neurons shape the traits of fast and slow muscle fibers in toads. “It was quite a failure,” says Szczupak, professor of physiology and cellular and molecular biology at the University of Buenos Aires. The work involved making cell cultures using fibers dissected from animals collected in the wild. But the cultures often became contaminated, so the work wasn’t progressing. “It was a very low point,” she says, recalling her frustration.
But then she met John Nicholls, a Stanford University neuroscientist and author of the book “Neurobiology of the Leech,” which makes the case that the invertebrate bloodsuckers are a useful model for studying the neural basis of locomotion, among other complex phenomena. Nicholls inspired Szczupak to attend a course on the animal at the Marine Biological Laboratory, and, once convinced of the worm’s potential, she switched her model.
Leeches have 21 midbody segments, or ganglia, each with its own set of sensory and motor neurons, and “each segment is exactly the same as the next,” Szczupak says. Additionally, “the movements are very clear; the neurons are huge and easy to study.” The simplicity of this body and motor plan makes it straightforward to perturb neurons and circuits and uncover how they contribute to movement.
For example, even without a brain or sensory inputs, individual ganglia can produce rhythmic motor activity and coordinate with one another to form a global network that drives movement, Szczupak found. But movement is also controlled locally: Each segment uses inhibitory input to modulate the activity of motor neurons, which shapes specific phases of crawling, she and her team reported earlier this year.
Szczupak spoke with The Transmitter about how leeches keep their balance, the movements they use that don’t need their brain, and what their simplicity can offer neuroscience.
This interview has been edited for length and clarity.
The Transmitter: What makes leeches a good model for studying the nervous system?
Lidia Szczupak: What is special about the leech is that it has very clear motor patterns that can be studied at the level of one segment, because one segment has to do the same as the next one. When you get information about one segment, you get information about the whole organism. But then, in order for the animal to survive and move around the world, the animal has to coordinate those segments.
TT: What specific aspect of motor control are you interested in?
LS: Leeches move either by swimming in the water or by crawling on surfaces. To do that, the animal has to produce a motor pattern that, for each segment, it has to elongate and contract. It does it for one segment, but then it has to be coordinated in an anteroposterior organization, so that the whole animal contracts and elongates in a coordinated manner. I study how the nervous system coordinates the signals that allow the animal to move.
TT: What have you learned about how leeches move?
LS: The animal organizes its movement by taking into consideration the necessary measures to keep its balance. The animal elongates its front part but leaves the center of mass in the back until it gets into a position where the animal feels safe, and then it moves its center of mass. The animal is not just mechanically elongating and contracting without any consideration other than the repeats of the movement.
TT: How does the nervous system coordinate that movement?
LS: One could think that the brain would coordinate all of the ganglia. We find that that’s not the case. Many of the coordinating signals are produced by the chain of ganglia without the brain. Then the signals that produce that coordination are sent forward and backward. Although the animal progresses its movement from anterior to posterior, it is as if the anterior ganglia are telling the posterior ganglia what to do, but then also the posterior ganglia tell the anterior ganglia, “Don’t start your movement before I finish mine.”
TT: How large is the leech field, and what other questions are the animals used for?
LS: At the time I trained as a postdoctoral researcher, the community was small but active. Unfortunately, today the number of laboratories that use the leech to study neurophysiological principles is very, very small. Many in the community have retired, including my postdoc advisor William Kristan. There is a group in Mexico that is working on how cells release neurotransmitters, but it is hard, especially with the lack of genetic tools. At this moment, science in general is very difficult; science with the leech is more difficult.
TT: What tools would help researchers studying leeches?
LS: A big step forward would be to be able to make the neurons express calcium sensors, which in Drosophila is trivial—you can make any cell express calcium sensors. In the leech, that is very difficult because their embryos are very small and have never been cultured outside of their cocoons, making it difficult to inject them with reagents.
TT: What do you think leeches can offer neuroscience?
LS: If you want to understand how networks really work, you need an animal in which your hypothesis can be checked in a very direct way. The tools we have in neuroscience today are very powerful at collecting massive amounts of information about neurons, but it is like going to a coffee shop, putting out sound sensors and trying to make sense of what society is talking about from the noise of multiple conversations. In the leech, you can sit at the table and listen to what the conversation is about.
