COORDINATED GULPING

Abstract

When C. elegans dine on bacteria, they Hoover up their meal quickly, and move on until they happen upon another bacterial colony. The nematodes gulp down their food by rhythmically contracting their muscular pharynx. Each stage of the contraction and relaxation cycle must be tightly coordinated as they gear up pumping from a few gulps per minute to five per second during a feast, otherwise the worm's pharynx blocks and the worm starves, even in the midst of plenty! The neurotransmitter serotonin also increases the pharynx's pumping frequency, but how it did this puzzled Timothy Niacaris and Leon Avery. Over the years, Avery's lab has built up a detailed understanding of the pump's physiology, identifying two neurons, MC and M3,that initiate the muscle's depolarisation and repolarisation, generating an action potential, which in turn initiates a contraction/relaxation cycle. But how serotonin functions to speed up pumping wasn't known. As shorter action potentials translate into faster pumping rates, Niacaris decided to measure how the muscle's action potential changed in response to serotonin. Working with nematodes where one or both of the nerves had been disconnected, Niacaris measured the muscle's action potential length in response to serotonin, and realised that the neurochemical coordinates faster pumping by altering the timing of the muscle's depolarisation and repolarisation(p. 223).Niacaris worked with three groups of mutated worms to see if he could find which aspects of the muscles control system serotonin was regulating. The first group had lost components of the M3 circuit and retained the MC circuit that drives depolarisation of the muscle and triggers the muscle to contract. The second group of worms had lost the MC circuit, but retained the M3 circuit that drives the muscle's repolarisation at the end of the action potential,and allows the muscle to relax. Both neurons had been disconnected in the third group. Niacaris measured how serotonin affected the duration of the pharynx muscle's action potential in each group of worms.When he tested worms that retained use of one neural circuit, serotonin shortened the action potential, proving that both neurons were involved in faster pumping. But Niacaris needed to rule out the possibility that serotonin also affected any other neural circuits that could also alter the action potential length, so he tested the worms where both neurons had been disconnected. If serotonin affected the action potential through other neural circuits, then the neurotransmitter could still shorten each action potential,even though MC and M3 were disconnected. But these worms' action potentials didn't change, so serotonin only affects two neural circuits to control the roundworm's rhythmic feeding response.Niacaris explains that it's relatively easy to understand how stimulating the M3 circuit with serotonin cuts the action potential length by swiftly repolarising the muscle, but it's less clear how altering the initial depolarisation also shortens the action potential. He adds that understanding how the tiny worms feed efficiently could help clinicians understand arrhythmia in the human heart. He explains that many of the key protein components that regulate the roundworm's pharynx have homologues in human heart muscle. So understanding how serotonin helps the round worm's pharynx to keep time could eventually help clinicians treat heart attacks by targeting the timing circuit to reset the heart's contraction clock.