The reaction to the infection shows the surprising flexibility of the nervous system | With news

Regardless of whether you are a person about the city or a worm in a dish, life can get all possible circumstances on your way. What you need is a nervous system that is flexible enough to deal with it. In a new study, the with neuroscientists show how even a simple animal can surround brain circuits and the chemical signals or “neuromodulators” in his brain in order to raise an adaptive reaction to an infection. The study can therefore offer a model for understanding how the brain in more complex organisms, including ourselves, creates what you have to cope with the postponement internal conditions.

“Neuromodulators play a central role in coupling changes in the inner states of animals to their behavior” Natural communication. “How combinations of neuromodulators, which are released from various neuronal sources, control different internal conditions that animals have, remains an open question.”

When C. Elegans Worms that were fed by contagious Pseudomonas Bacteria ate less and became lethargic. When the researchers looked over the nervous system to see how this behavior happened, they found that the worm was completely revealed by the roles of several of its 302 neurons and some of the peptides that they had secretly secreted in the brain in order to modulate behavior. Systems that reacted to stress in a case or in a different feeling of satiety were to be dealt with.

“This is a question of how to adapt to their surroundings, with the highest flexibility in view of the series of neurons and neuromodulators that they have” Natural communication. “How can you provide the maximum options that are available to you?”

Research that was found took place in the laboratory of the senior author Steve Flavell, an extraordinary professor at the Picow Institute for Learning and Memory, and the department for brain and cognitive and cognitive sciences and a researcher from the Howard Hughes Medical Institute. Pradhan, who was supported by a scholarship between the K. Lisa Yang Brain-Body Center during the work, has teamed up with the former student of the Flavell Lab, Gurrein Madan, to lead research.

According to Pradhan, the team discovered several surprises in the course of the study, including the fact that a neuropeptide called FLP-13 completely turned its function on infected animals and animals that suffer other stress forms. Earlier studies had shown that a neuron called ALA, when worms are stressed by heat, released FLP-13 so that worms go alone, a sleep-like state. But when the worms ate in the new study Pseudomonas Bacteria, a gang of other neurons, found FLP-13 free to combat the calm so that the worms can survive longer. In the meantime, ALA took on a completely different role during the illness: the load led to the suppression of feeding by issuing another group of peptides.

A comprehensive approach

In order to understand how the worms reacted to an infection, the team followed many characteristics of the behavior of the worms and made genetic manipulations to examine the underlying mechanisms. They also recorded activities across the entire brain of the worms. This type of extensive observation and experiments are difficult to achieve in more complex animals, but C. Elegans' Relative simplicity makes it a follow -up test bed, says Pradhan. The team's approach also made it possible to meet so many unexpected knowledge.

For example, Pradhan did not suspect that the ALA neuron would turn out to be the neuron that suppressed feeding, but when she observed her behavior long enough, she began to see that the reduced feeding from the worms arose that would normally not take. Since she and Madan manipulated more than a dozen genes, of which they thought they could influence the behavior and feed in the worm, she opened another one she took up CEH-17 That she had read about years ago that seemed to promote seizures of “Microsleep” in the worms. When she excluded CEH-17In contrast to normal animals, they found that these worms did not reduce feeding than they were infected. It just happens like that CEH-17 It is specially needed to ensure that ALA works properly. Then the team was recognized that ALA may be involved in the behavior of the feeding reduction.

To know safely, they then excluded the various peptides that Ala releases, and saw it when they were three in particular. FLP-24, NLP-8 And FLP-7Infected worms showed no reduced feeding in infections. This won that ALA drives the reduced feeding behavior through emissions of these three peptides.

In the meantime, the screens of Pradhan and Madan also showed that infected worms were missing FLP-13They would go into resting state much earlier than infected worms with the available peptide. Remarkably, the worms, who fought out the idle state, lived longer. They found that fighting the calm depending on the FLP-13, which comes from four neurons (i5, I1, Ash and Oll), but not on ala. Other experiments showed that FLP-13 worked on a widespread neuropeptic receptor called DMSR-1 to prevent peace.

Make a little nap

The last big surprise of the study was that the rest period Pseudomonas Infection in worms is not the same as other forms of drowsiness that appear in other contexts, such as: B. after feeling saturation or heat stress. In these cases, worms are not easy (with a little browse), but in the middle of the infection their calm was slightly reversible. It seemed more lethargy than sleep. Using the ability of the laboratory during the behavior, Pradhan and Madan found that a neuron called ASI was particularly active during the lethargy comrades. This observation continued to solidify when they showed that ASIS secretion of the Peptide DAF-7 was necessary so that the calm appeared in infected animals.

Overall, the study showed that the worms restore and reconfigure the functions of neurons and peptides – sometimes up to the completely reverse point – in order to increase an adaptive reaction to an infection compared to another problem such as stress. The results therefore shed light on a difficult question that was to be solved. How do the brain use your repertoire of cells, circuits and neuromodulators to deal with what life gives you? At least part of the answer seems to be in redesigning existing components instead of creating unique for every situation.

“The conditions of stress, saturation and infection are not induced by unique sentences of neuromodulators,” the authors wrote in their work. “Instead, a larger sentence of neuromodulators from different sources and in different combinations can be used to specify these different internal conditions.”

In addition to Pradhan, Madan and Flavell, the other authors of paper di Kang, Eric Bueno, Adam Atanas, Talya Kramer, Ugur Dag, Jessica Lage, Matthew Gomes, Alicia Kun-Yang Lu and Junggyeon Park.

The support for research came from the Picower Institute, the Freedom Together Foundation, the K. Lisa Yang Brain-Body Center and the Yang Tan collective on; the national health institutes; The McKnight Foundation; The Alfred P. Sloan Foundation; And the Howard Hughes Medical Institute.