The brain can recall and awaken past immune responses

V published On November 8, neuroimmunologists showed that the immune response can be elicited by stimulating neurons in the insular cortex of the brain. In other words, it looks like the identified I.P. Pavlov, the conditioning of reactions also applies to immunity. We tell the details to the start of the flagship Data Science course…

Using state-of-the-art genetics tools, her team at the Technion in Haifa, Israel, has identified neurons in mice that are activated during experimentally induced abdominal inflammation. Researchers have shown that repeated stimulation of the same neurons can cause the same types of inflammation again.

“This is an outstanding work,” said Kevin Tracy, neurosurgeon and president of the Feinstein Institute for Medical Research in Manhasset, New York. “It confirms that the classical concept of immunological memory can be represented in neurons.” Previously, scientists only assumed that the brain could remember and retrieve immune responses. According to Kevin Tracy, Asya Rolls proved it.

Ruslan Medzhitov, an immunologist at the Yale School of Medicine in New Haven, Connecticut, said the new study was “very provocative.” But unlike other groundbreaking research that pushes boundaries and challenges conventional wisdom, this research elicits a “Oh, that makes sense.” Decades of research and everyday experience provide vivid examples of mind-body interactions.

Around the time Pavlov was experimenting with dogs, American physician John Mackenzie observed how his patient’s throat itched at the sight of an artificial rose and had difficulty breathing. It is assumed that the sensation of the presence of pollen is already enough to trigger allergy symptoms.

In the 1970s, scientists discovered a similar phenomenon in experiments on rats. They have given animals an immune-suppressing drug many times, along with saccharin, an artificial sweetener. After that, the activity of the immune system was suppressed by saccharin alone.

Many will remember the moments when the smell of food, from which we were not well, again caused unpleasant sensations. But until now, the mechanism responsible for these reactions has remained in the shadows.

“Such experiences” cannot be based on immunological memory as we know it, “says Rolls. “It looks like these reactions start in the brain. Somehow, thoughts trigger physiological processes. “

In recent years, Asi Rolls lab has been understanding how thoughts and emotions can affect physical health. In 2018, the team reported that stimulating neurons in mice in reward brain centers disables a subset of immune cells that suppress the body’s defenses. Tumors grow in surviving mice slower…

In a study published in May, the Rolls team found that activation of certain nerves in the colon prevents immune cells from entering the tissue from the bloodstream. This suggests a mechanism control local inflammation of the brain.

Given that these groups of neurons regulate immune activity so precisely, Rolls could not imagine that the brain could control the system without knowing its state. “So we wanted to see how the brain represents the state of the immune system,” she said. The team focused on the insular cortex, a structure deep in the brain that processes pain, emotion, and internal physical sensations in the body.

“It’s logical to assume that the immune system may be part of this introceptive information,” says Rolls.

To find out if this was the case, the researchers mixed the drinking water of the lab mice with a chemical that caused the mice to have colitis for a week. This chemical disrupted the lining of the colon – immune cells spilled over into the damage, which then spiraled out of control.

Genetic modification of the mice allowed scientists to mark the neurons active on the day of the peak of inflammation with fluorescent, highlighting the cells in the islet. Then they placed a molecular switch on the activated islet cells and waited.

A few weeks after the muscles had recovered, the researchers turned on the neurons again, causing a similar inflammatory response in the colon. The same results were observed in mice with peritonitis.

The immune responses triggered by neural stimulation, Rolls said, resembled the original state of the disease. The similarity reaches the molecular level: in mice with induced peritonitis, the number of leukocytes, which carry a specific receptor protein, increased in the abdominal cavity during the first and repeated inflammation.

The researchers also observed the opposite effect: the symptoms of the disease in animals were easier when the initial set of activated neurons was suppressed by the scientists. This suggests that even when the inflammation is chemical, its severity can be determined by signals from the brain.

After a series of nerve mapping experiments, the team determined that the insular cortical neurons that fired up during the initial inflammation “actually have the ability to transmit a message all the way down to the colon,” Rolls said.

According to Tracy, the new study shows that “you cannot separate the state of neuronal activity from the state of activity of the immune system. This is a two-way street. “

In 2002, Tracy and his colleagues pioneered a new direction in this area. They discoveredthat the brain can send anti-inflammatory signals to other parts of the body via the vagus nerve.

This line of research has advanced so much that today bioelectronic devices are being developed and studied that control inflammation in rheumatoid arthritis, pulmonary hypertension and other diseases.

However, unlike the vagus nerve system, the neurons of the insular lobe in the Rolls mechanism sense inflammation, remember the state of immunity and can cause this state again. According to Ruslan Medzhitov, this behavior is more like Pavlov’s conditioning than a negative feedback reaction.

Tracy thinks that the vagus nerve is like the brake line of a car. Rolls research shows that “there is a driver,” he says. “There is someone who decides which to press the pedal, brake or gas.”

Rolls and her colleagues cannot yet say whether the “memory” of the neurons in the islet of inflammation describes the immune response itself, or if it is a recording of the sensations of the inflamed body tissues. In other words, the memory of how it feels to be sick with inflammation. Scientists do not exclude that other parts of the brain may be involved in memorizing the immune response.

Research can have far-reaching implications. Describing the anatomical pathway that connects “your emotional state with inflammation in the colon,” Medzhitov shared his opinion: “In my opinion, this is probably the best demonstration of psychosomatic control.” In addition, the results of the study contradict the common idea of the brain working “from top to bottom”.

“Most people tend to think, ‘We’re smart and we decide what to do,’ and then we force the body to do it,” says Tracy. “But that’s not how the nervous system works.”

The brain receives and synthesizes information about infection, fever, and then gives an answer. Rolls’ work, Tracy says, shows that the brain is inseparable from the immune system. In the meantime, biological neurons reveal their secrets, take a look at our courses to learn how to solve business problems using artificial neural networks.