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The Brain Has a ‘Low-Power Mode’ That Blunts Our Senses

The Brain Has a ‘Low-Power Mode’ That Blunts Our Senses

Since leptin is released by fat cells, scientists believe its presence in the blood is likely to signal to the brain that the animal is in an environment where food is ample and there’s no need to conserve energy. The new work suggests that low levels of leptin alert the brain to the malnourished state of the body, switching the brain into low-power mode.

“These results are unusually satisfying,” said Julia Harris, a neuroscientist at the Francis Crick Institute in London. “It is not so common to obtain such a beautiful finding that is so in line with the existing understanding,”

Distorting the Neuroscience?

A significant implication of the new findings is that much of what we know about how brains and neurons work may have been learned from brains that researchers unwittingly put into low-power mode. It is extremely common to restrict the amount of food available to mice and other experimental animals for weeks before and during neuroscience studies to motivate them to perform tasks in return for a food reward. (Otherwise, animals would often rather just sit around.)

“One really profound impact is that it clearly shows that food restriction does impact brain function,” said Rochefort. The observed changes in the flow of charged ions could be especially significant for learning and memory processes, she suggested, since they rely on specific changes happening at the synapses.

“We have to think really carefully about how we design experiments and how we interpret experiments if we want to ask questions about the sensitivity of an animal’s perception, or the sensitivity of neurons,” Glickfeld said.

The results also open up brand-new questions about how other physiological states and hormone signals could affect the brain, and whether differing levels of hormones in the bloodstream might cause individuals to see the world slightly differently.

Rune Nguyen Rasmussen, a neuroscientist at the University of Copenhagen, noted that people vary in their leptin and overall metabolic profiles. “Does that mean, then, that even our visual perception—although we might not be aware of it—is actually different between humans?” he said.

Rasmussen cautions that the question is provocative, with few solid hints to the answer. It seems likely that the conscious visual perceptions of the mice were affected by food deprivation because there were changes in the neuronal representations of those perceptions and in the animals’ behaviors. We can’t know for sure, however, “since this would require that the animals could describe to us their qualitative visual experience, and obviously they cannot do this,” he said.

But so far there also aren’t any reasons to think that the low-power mode enacted by the visual cortical neurons in mice, and its impact on perception, won’t be the same in humans and other mammals.

“These are mechanisms that I think are really fundamental to neurons,” Glickfeld said.

Editor’s note: Nathalie Rochefort is a member of the board of the Simons Initiative for the Developing Brain, which is funded by the Simons Foundation, the sponsor of this editorially independent magazine. Maria Geffen is a member of the advisory board for Quanta.

Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

A Brain Chemical Helps Neurons Know When to Start a Movement

A Brain Chemical Helps Neurons Know When to Start a Movement

By washing through the brain, neuromodulators “allow you to govern the excitability of a large region of the brain more or less in the same way or at the same time,” said Eve Marder, a neuroscientist at Brandeis University widely recognized for her pioneering studies on neuromodulators in the late 1980s. “You’re basically creating either a local brain wash or more extended brain wash that is changing the state of a lot of networks simultaneously.”

The powerful effects of neuromodulators mean that abnormal levels of these chemicals can lead to numerous human diseases and mood disorders. But within their optimal levels, neuromodulators are like secret puppeteers holding the strings of the brain, endlessly shaping circuits and shifting activity patterns into whatever may be most adaptive for the organism, moment by moment.

“The neuromodulatory system [is] the most brilliant 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 diffuse signal … but the effects are precise.”

Shifting Brain States

In the past few years, a burst of technological advances has paved the way for neuroscientists to go beyond studies of neuromodulators in small circuits to studies looking across the whole brain in real time. They have been made possible by a new generation of sensors that modify the metabotropic neuronal receptors—making them light up when a specific neuromodulator lands on them.

Yulong Li

The researcher Yulong Li of Peking University in Beijing has developed a number of sensors that are advancing studies of neuromodulators and their effects.Photograph: Tianjun Zhao

The lab of Yulong Li at Peking University in Beijing has developed many of these sensors, beginning with the first sensor for the neuromodulator acetylcholine in 2018. The team’s work lies in “harnessing nature’s design” and taking advantage of the fact that these receptors have already evolved to expertly detect these molecules, said Li.

Jessica Cardin, a neuroscientist at Yale University, calls the recent studies using these sensors “the tip of the iceberg, where there’s going to be this enormous wave of people using all of those tools.”

In a paper posted in 2020 on the preprint server bioarxiv.org, Cardin and her colleagues became the first to use Li’s sensor to measure acetylcholine across the entire cortex in mice. As a neuromodulator, acetylcholine regulates attention and shifts brain states related to arousal. It was widely believed that acetylcholine always increased alertness by making neurons more independent of the activity in their circuits. Cardin’s team found that this holds true in small circuits with only hundreds to thousands of neurons. But in networks with billions of neurons the opposite occurs: Higher levels of acetylcholine lead to more synchronization of activity patterns. Yet the amount of synchronization also depends on the region of the brain and the arousal level, painting the picture that acetylcholine does not have uniform effects everywhere.

Another study published in Current Biology last November similarly upended long-held notions about the neuromodulator norepinephrine. Norepinephrine is part of a monitoring system that alerts us to sudden dangerous situations. But since the 1970s, it’s been thought that norepinephrine is not involved in this system during certain stages of sleep. In the new study, Anita Lüthi at the University of Lausanne in Switzerland and her colleagues used Li’s new norepinephrine sensor and other techniques to show for the first time that norepinephrine doesn’t shut down during all stages of sleep, and indeed plays a role in rousing the animal if need be.