Scientists discovered a brain circuit that coordinates speaking and breathing

When mammals make sounds with their voices, this must match their Breathing. This is because the sounds are made in the airway. Previous research has found parts of the brain that control making sounds, but we still don’t know which brain cells are in charge of bringing the vocal cords together and making sure breathing and making sounds happen simultaneously.

A new study by MIT scientists investigated the neuronal circuit directly mediating vocal production and vocal-respiratory coupling in mice. This brain circuit drives vocalization and ensures that you talk only when you breathe out and stop talking when you breathe in.

The newly discovered brain circuit regulates two critical vocalization processes: constricting the larynx and expelling air from the lungs. The important thing is that a particular region of the brainstem that regulates breathing rhythm controls this vocalization circuit. This guarantees that breathing always takes precedence over speaking.

Fan Wang, an MIT professor of brain and cognitive sciences, a member of MIT’s McGovern Institute for Brain Research, and the senior author of the study, said, “When you need to breathe in, you have to stop vocalization. We found that the neurons that control vocalization receive direct inhibitory input from the breathing rhythm generator.”

The vocal cords are two muscle bands located in the larynx. They can open and close. When mostly closed or brought together, air exhaled from the lungs creates a sound as it passes through them.

The MIT team’s investigation aimed to learn how the brain controls the vocalization process. They investigated this with mice as ultrasonic vocalizations (USVs) are sounds used to communicate with one another. The mice’s distinctive whistling mechanism is created when they exhale air through a tiny gap between their virtually closed vocal cords.

Scientists are keen to understand the neurons that control vocal cord adduction and how those neurons interact with the breathing circuit. Scientists used a technique that enables mapping the synaptic connections between neurons to find out. They started by tracing backward to identify the neurons that innervate the laryngeal motor neurons, which are known to drive vocal cord adduction.

This research revealed that a key source of vocalization input comes from a group of premotor neurons found in a hindbrain region called the retroambiguus nucleus (RAm). While previous studies knew this area was involved in vocalization, they didn’t know exactly which part was needed or how it helped produce sound.

The scientists discovered that these RAm neurons were strongly active during ultrasonic vocalizations (USVs). They then focused on these vocalization-specific RAm neurons, called RAmVOC, using techniques like chemogenetics and optogenetics to understand their role. When they blocked these neurons, the mice couldn’t produce any vocalizations. Their vocal cords didn’t close, and their abdominal muscles didn’t contract as they usually do during exhalation for vocalization.

On the other hand, when the RAmVOC neurons were activated, the vocal cords closed, the mice exhaled, and USVs were produced. However, if the stimulation lasted for two seconds or longer, inhalations would interrupt the vocalizations, suggesting that the process is controlled by the same part of the brain that regulates Breathing.

Wang said, “Breathing is a survival need. Even though these neurons are sufficient to elicit vocalization, they are controlled by Breathing, which can override our optogenetic stimulation.”

Further synaptic mapping showed that the RAmVOC neurons get direct inhibitory input from neurons in the pre-Bötzinger complex, a region of the brainstem that functions as an inhalation rhythm generator.

The pre-Bötzinger complex automatically and continuously generates inhalation rhythms, and the inhibitory neurons in that region project to these vocalization premotor neurons, effectively shutting them down. This ensures that Breathing remains dominant over speech production and that we have to pause to breathe while speaking.

Scientists have identified a conserved circuit in mice that plays a role in human speech production and breathing.

Jaehong Park, a Duke University graduate student who is currently a visiting student at MIT, said, “Even though the exact mechanism and complexity of vocalization in mice and humans is different, the fundamental vocalization process, called phonation, which requires vocal cord closure and the exhalation of air, is shared in both the human and the mouse.”

Journal Reference:

Jaehong Park, Seonmi Choi et al. Brainstem control of vocalization and its coordination with respiration. Science. DOI: 10.1126/science.adi8081

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