A team led by a City University of Hong Kong (CTU) neuroscientist has identified a key mechanism of a biological clock that keeps roundworms stable by defecating at regular intervals.

The excretory phase is under timed control of A nerve A cell located on the head of a worm. This cell fire a Nerve impulse, or burst of electrical discharge, every 45 seconds or so. Each impulse is immediately transmitted along the worm through a nerve fiber that connects to a nerve cell in the tail. This cell emits an impulse with a synchronous impulse from the head nerve cell, which stimulates the lower-intestinal muscles to expel stool.

“The 1-millimeter-long roundworm Caenorhabditis elegans, or C. elegans, is used as a model organism by biologists around the world. Wild-type worms, in the presence of abundant food, eat non-stop. Defecate every 45 seconds with almost clock-like precision. Why and How Worms Learn About Its Basic Mechanisms “Attracted researchers to study,” said team co-leader Dr. Liu Qiang says. “Our findings solve this 30-year mystery, deepen our understanding of rhythmic behavior, and deepen the relationship between the animal’s nervous system and physiology.”

CITU’s Dr. Liu Qiang and Dr. Peking University. The research was jointly led by Luis Tao. The results published on 19 May 2022 Nature communicationentitled “C. elegans enteric motor neurons fire synchronized”. Action potential Basis of the Excretory Motor Program.”

The gut-brain circuit

C. Elegance is also well studied in neuroscience Brain researchAnd all 302 cells Its nervous system has been identified, named and physically mapped along with all their nerve connections. The two main neurons involved in controlling bowel movements are the AVL in the head and the DVB in the tail.

“Researchers knew that C. elegans produces periodic surges of calcium in gut epithelium cells called calcium waves, which trigger the release of gut neuropeptides that stimulate AVL and DVB neurons, leading to bowel movement. However, the underlying mechanisms of communication between the gut and the brain were unknown. Two enteric neurons, one in the worm’s head and one in the other How do they communicate with each other over such a distance while processing the timing signal from the tail and gut with remarkable robustness and precision?” Dr. Liu says. “For the first time, we showed that AVL and DVB neurons generate all-or-none impulses, or action potentials, and this digital signaling allows AVL to instantaneously communicate long-distance with DVB in the head. Control faecal excretion.”

the reason Calcium ions Jumping into the cell between each nerve impulse, the researchers examined AVL-to-DVB signaling under a special microscope using videoworms programmed to glow fluorescent green in the presence of calcium. They first observed a general wave of calcium moving through the gut. After about 3 seconds, they found nearly simultaneous calcium spikes in AVL and DVB that lasted half a second and repeated once every 45 seconds (see Figure 1).

Calcium spikes in AVL and DVB coincided with head-to-tail muscle movements that occurred at approximately the same time as stool ejection. From these findings, the researchers conclude that although the gut itself is the general defecation pacemaker, synchronized AVL and DVB impulses control the precise timing and coordination of head-to-tail body and gut movements required for the voiding phase.

Multitasking capability

Direct measurements of voltage across the membrane of isolated AVL and DVB cells confirmed the spike profiles of their action potentials. Closer examination reveals that the AVL impulse is an abnormal action potential consisting of two spikes in close proximity. The first spike acts as a positive, fast signal (signal increase in about 100 milliseconds, red circle in Figure 2) that propagates rapidly (in milliseconds) to the DVB and changes in the sequence of muscle movements leading to defecation. The second spike acts as a negative, slow signal (in seconds, yellow circle in Figure 2) that switches off the sequence to prevent further bowel movements and prevent excessive bowel movements. Also, a long negative undershoot phase (tens of seconds, green circle in Figure 2) after each AVL pulse prevents DVB misfiring impulses when they are not needed.

“The head AVL neuron plays the most critical role in regulating bowel rhythms over multiple time scales,” Dr. Liu says. “It not only relays, it also modulates the pacemaker signal from the gut by resetting the system with each bowel movement and prevents the nerve from misfiring between cycles, thus keeping the body clock strong and accurate.”

The study paves the way for further research into gut-brain communication and other body clock systems that underlie repetitive animal behavior. “I have no doubt that the basic principles of brain function learned from the study of worms can be used as a springboard for understanding more complex brains like ours,” said Dr. Liu adds.