How the brain generates rhythmic behavior

Many of our bodily functions, such as walking, breathing, and chewing, are controlled by brain circuits called central oscillators, which generate rhythmic firing patterns that regulate these behaviors.

MIT neuroscientists have now discovered the neuronal identity and mechanism underlying one of these circuits: an oscillator that controls the rhythmic back-and-forth sweeping of tactile whiskers, or whisking, in mice. This is the first time that any such oscillator has been fully characterized in mammals.

The MIT team found that the whisking oscillator consists of a population of inhibitory neurons in the brainstem that fires rhythmic bursts during whisking. As each neuron fires, it also inhibits some of the other neurons in the network, allowing the overall population to generate a synchronous rhythm that retracts the whiskers from their protracted positions.

"We have defined a mammalian oscillator molecularly, electrophysiologically, functionally, and mechanistically," says Fan Wang, an MIT professor of brain and cognitive sciences and a member of MIT's McGovern Institute for Brain Research. "It's very exciting to see a clearly defined circuit and mechanism of how rhythm is generated in a mammal."

Wang is the senior author of the study, which appears today in Nature. The lead authors of the paper are MIT research scientists Jun Takatoh and Vincent Prevosto.

Rhythmic behavior

Most of the research that clearly identified central oscillator circuits has been done in invertebrates. For example, Eve Marder's lab at Brandeis University found cells in the stomatogastric ganglion in lobsters and crabs that generate oscillatory activity to control rhythmic motion of the digestive tract.

Characterizing oscillators in mammals, especially in awake behaving animals, has proven to be highly challenging. The oscillator that controls walking is believed to be distributed throughout the spinal cord, making it difficult to precisely identify the neurons and circuits involved. The oscillator that generates rhythmic breathing is located in a part of the brain stem called the pre-Bötzinger complex, but the exact identity of the oscillator neurons is not fully understood.

"There haven't been detailed studies in awake behaving animals, where one can record from molecularly identified oscillator cells and manipulate them in a precise way," Wang says.

Whisking is a prominent rhythmic exploratory behavior in many mammals, which use their tactile whiskers to detect objects and sense textures. In mice, whiskers extend and retract at a frequency of about 12 cycles per second. Several years ago, Wang's lab set out try to identify the cells and the mechanism that control this oscillation.

To find the location of the whisking oscillator, the researchers traced back from the motor neurons that innervate whisker muscles. Using a modified rabies virus that infects axons, the researchers were able to label a group of cells presynaptic to these motor neurons in a part of the brainstem called the vibrissa intermediate reticular nucleus (vIRt). This finding was consistent with previous studies showing that damage to this part of the brain eliminates whisking.

The researchers then found that about half of these vIRt neurons express a protein called parvalbumin, and that this subpopulation of cells drives the rhythmic motion of the whiskers. When these neurons are silenced, whisking activity is abolished.

Next, the researchers recorded electrical activity from these parvalbumin-expressing vIRt neurons in brainstem in awake mice, a technically challenging task, and found that these neurons indeed have bursts of activity only during the whisker retraction period. Because these neurons provide inhibitory synaptic inputs to whisker motor neurons, it follows that rhythmic whisking is generated by a constant motor neuron protraction signal interrupted by the rhythmic retraction signal from these oscillator cells.

"That was a super satisfying and rewarding moment, to see that these cells are indeed the oscillator cells, because they fire rhythmically, they fire in the retraction phase, and they're inhibitory neurons," Wang says.

"New principles"

The oscillatory bursting pattern of vIRt cells is initiated at the start of whisking. When the whiskers are not moving, these neurons fire continuously. When the researchers blocked vIRt neurons from inhibiting each other, the rhythm disappeared, and instead the oscillator neurons simply increased their rate of continuous firing.

This type of network, known as recurrent inhibitory network, differs from the types of oscillators that have been seen in the stomatogastric neurons in lobsters, in which neurons intrinsically generate their own rhythm.

"Now we have found a mammalian network oscillator that is formed by all inhibitory neurons," Wang says.

The MIT scientists also collaborated with a team of theorists led by David Golomb at Ben-Gurion University, Israel, and David Kleinfeld at the University of California at San Diego. The theorists created a detailed computational model outlining how whisking is controlled, which fits well with all experimental data. A paper describing that model is appearing in an upcoming issue of Neuron.

Wang's lab now plans to investigate other types of oscillatory circuits in mice, including those that control chewing and licking.

Read more at Science Daily

Novel brainstem circuit gives rise to the rhythms of vocalization

The vocal sounds of humans -- laughing, crying, and the babbling of babies -- have the same rhythmic quality as the sounds made by many mammals, songbirds, and even some species of fish. Researchers at UC San Francisco have discovered that a small cluster of neurons in the brain stem not only regulates tempo but also coordinates vocalization with breathing.

"Just to laugh or shout, the body has to coordinate about 100 different muscles in a rhythmic pattern within a single breath," said Kevin Yackle, MD, PhD, a Sandler Faculty Fellow and senior author of the study published online Jan. 7, 2022, in Neuron. "We discovered the neurons that, when switched on, give us this unconscious ability."

It's been widely understood that many animals, including humans, have innate control of breathing -- you don't have to use your brain to do it. Yackle and his team suspected that the same control exists for innate vocalizations.

To confirm the existence of this brain circuit, Yackle and his team studied the sounds made by baby mice when they were separated from their mothers. The babies' cries had a recognizable pattern associated with specific muscle movements. The researchers then determined which cells in the brain stem were responsible for this rhythm, which turned out to be a previously unknown circuit that appears to control the breath and coordinate the muscles needed to produce the vocal sounds.

Identifying this system will enable scientists to ask new questions about how we speak and why some people have trouble doing it.

A New Perspective on Speech Pathologies

"It could be that when we're learning to speak, we're learning to either bypass this system or to directly control it," Yackle said. "Altered wiring in this pattern-generating system could cause speech pathologies."

Yackle and his team are intrigued by studies suggesting that early in their lives, children with autism innately produce different kinds of sounds than other children do. Some children with autism are either unable to speak or have difficulty producing and understanding the tones and rhythms of speech.

Yackle and his team are intrigued by studies suggesting that early in their lives, children with autism innately produce different kinds of sounds than other children do. Some children with autism are either unable to speak or have difficulty producing and understanding the tones and rhythms of speech.

Such speech pathologies are often viewed as an inability to learn how to talk, said Yackle. He is flipping that perspective on its head, asking whether the speech problems are less about learning and more about the brain circuit controlling speech.

"A child may be hearing and learning language, but if the system that allows them to vocalize is different in some way, they just may not be able to coordinate the breath and movements to make the sounds," he said. "If we know how that system is different, it might change how we'd teach some people to speak."

Read more at Science Daily

That primate’s got rhythm!

Songbirds share the human sense of rhythm, but it is a rare trait in non-human mammals. An international research team led by senior investigators Marco Gamba from the University of Turin and MPI’s Andrea Ravignani set out to look for musical abilities in primates. “There is longstanding interest in understanding how human musicality evolved, but musicality is not restricted to humans”, says Ravignani. “Looking for musical features in other species allows us to build an ‘evolutionary tree’ of musical traits, and understand how rhythm capacities originated and evolved in humans.”

To find out whether non-human mammals have a sense of rhythm, the team decided to study one of the few ‘singing’ primates, the critically endangered lemur Indri indri. The researchers wanted to know whether indri songs have categorical rhythm, a ‘rhythmic universal’ found across human musical cultures. Rhythm is categorical when intervals between sounds have exactly the same duration (1:1 rhythm) or doubled duration (1:2 rhythm). This type of rhythm makes a song easily recognisable, even if it is sung at different speeds. Would indri songs show this “uniquely human” rhythm?

Ritardando in the rainforest

Over a period of twelve years, the researchers from Turin visited the rainforest of Madagascar to collaborate with a local primate study group. The investigators recorded songs from twenty indri groups (39 animals), living in their natural habitat. Members of an indri family group tend to sing together, in harmonised duets and choruses. The team found that indri songs had the classic rhythmic categories (both 1:1 and 1:2), as well as the typical ‘ritardando’ or slowing down found in several musical traditions. Male and female songs had a different tempo but showed the same rhythm.

According to first author Chiara de Gregorio and her colleagues, this is the first evidence of a ‘rhythmic universal’ in a non-human mammal. But why should another primate produce categorical ‘music-like’ rhythms? The ability may have evolved independently among ‘singing’ species, as the last common ancestor between humans and indri lived 77.5 million years ago. Rhythm may make it easier to produce and process songs, or even to learn them.

Endangered species

“Categorical rhythms are just one of the six universals that have been identified so far”, explains Ravignani. “We would like to look for evidence of others, including an underlying ‘repetitive’ beat and a hierarchical organisation of beats—in indri and other species.” The authors encourage other researchers to gather data on indri and other endangered species, “before it is too late to witness their breath-taking singing displays.”

From Science Daily