By cleansing the brain, neuromodulators “allow you to control the excitability of large areas of the brain in more or less the same way or at the same time,” says Brandeis University neuroscientist Eve Marder, widely recognized for her groundbreaking research. . About neuromodulators in the late 1980s. “You’re basically creating local brainwashing or broader brainwashing while changing the state of many networks.”

The powerful effects of neuromodulators mean that abnormal levels of these chemicals contribute to many human diseases and mood disorders. But at their optimum level, neuromodulators act like secret puppets manipulating the brain, endlessly shaping circuits and shifting activity patterns into whatever might be best for the organism, moment by moment.

“Neuromodulation system [is] The best hack you can imagine,” said Mac Shine, a neurobiologist at the University of Sydney. “Because what you’re doing is you’re sending a very, very scattered signal…but the effect is precise. “

change the state of the brain

Over the past few years, a series of technological advancements has paved the way for neuroscientists to expand from the study of neuromodulators in small circuits to those looking at the entire brain in real time. A new generation of sensors can modify metabotropic neuronal receptors, enabling them to light up when specific neuromodulators land on them.

Peking University researcher Yulong Li has developed a number of sensors that are advancing research into neuromodulators and their effects.Photograph: Tianjun Zhao

Li Yulong’s lab at Peking University has developed many such sensors, starting with the first neuromodulator acetylcholine sensor in 2018. The team’s work lies in “using nature’s design” and using these receptors that have evolved to expertly detect these molecules, Li said.

Yale neuroscientist Jessica Cardin called recent research using these sensors “the tip of the iceberg, and there’s going to be a huge number of people using all these tools.”

In a paper published on the preprint server bioarxiv.org in 2020, Cardin and her colleagues became the first to use Li’s sensor to measure acetylcholine in the entire cortex of mice. As a neuromodulator, acetylcholine regulates attention and alters brain states associated with arousal. It is widely believed that acetylcholine always increases alertness by making neurons more independent of activity in their circuits. Cardin’s team found that this holds true in small circuits with only hundreds or thousands of neurons. But in networks with billions of neurons, the opposite is true: the higher the level of acetylcholine, the more synchronized the patterns of activity. However, the amount of synchronization also depends on brain region and arousal level, depicting that acetylcholine does not have a uniform effect everywhere.

Another study was published in Current Biology Last November also upended long-held beliefs about the neuromodulator norepinephrine. Norepinephrine is part of the surveillance system that alerts us to sudden, dangerous situations. But since the 1970s, it has been thought that norepinephrine is not involved in the system during certain stages of sleep. In the new study, Anita Lüthi of the University of Lausanne in Switzerland and her colleagues used Li’s new norepinephrine sensor and other technologies to demonstrate for the first time that norepinephrine does not turn off during all stages of sleep, and does indeed turn off if needed. , wake up the animal.