Mice use almost completely distinct sets of neurons for their two different types of vocalizations – the squeaks they produce when in distress or fighting, and the whistle-like ultrasonic vocalizations they use when communicating socially, Cornell neuroscientists have found.
The discovery is a step toward understanding how the brain is organized to control vocalization in mammals, including humans.
“Our ability to produce different vocal sounds is critical to our social identity and the ability to communicate,” said Katherine Tschida, the Mary Armstrong Meduski ’80 Assistant Professor of psychology in the College of Arts and Sciences (A&S), whose lab studies motor control of vocalization. “Whether you’re a human producing speech or laughter or a mouse producing social vocalizations or squeaks, mammals have a limited set of hardware in their brainstems underlying our ability to produce these vocal communication sounds.”
In mice, nonoverlapping sets of neurons in the brainstem are active in association with the two distinct types of vocalization: squeaks vs. ultrasonic vocalizations, Tschida said. Different mammals and vertebrates are likely to have a lot in common, she and collaborators believe, so they’ve been working on identifying neurons that are important for producing vocalizations.
Tschida is the corresponding author of “Production of Mouse Ultrasonic Vocalizations and Distress Calls is Associated with Different Patterns of Fos Expression in the Nucleus Retroambiguus,” published Aug. 17 in eNeuro. Co-first authors are doctoral student Patryk Ziobro, M.A. ’23, and postdoctoral researcher Da-Jiang (David) Zheng.
In this study, the researchers focused on the nucleus retroambiguus (RAm) region of the brainstem, which is located close to the spinal cord. It’s known to be important for vocalization through its connection to respiration and larynx control – in nonhuman animals and in humans.
The RAm region has been studied in connection with mouse ultrasonic vocalizations but has not been studied in relation to mouse squeaking before, Tschida said, nor for a direct comparison between squeaking versus ultrasonic vocalizations.
“We asked, if we make a mouse produce a high rate of squeaks, how do things light up?” she said. “We fully expected we would see a similar pattern to what you get in a mouse producing a high rate of social vocalizations. But when we looked at the data, we saw that the pattern looked completely different.”
The team elicited high levels of social ultrasonic vocalizations in mice by introducing an unknown female mouse. Lots of sniffing, following and curious ultrasonic chatter ensued as the mice investigated one another. To elicit high levels of squeaking, the researchers tapped into the mice’s natural courtship behavior, Tschida said: Female mice squeak a lot when being vigorously courted by a male, both when they’re sexually receptive and when they’re not.
The researchers assessed brain activity during vocalizations of both types by visualizing the expression of Fos, an immediate early gene protein that can be used as a proxy for recent neural activity. Mice that had produced squeaks and mice that had produced ultrasonic vocalizations showed strikingly different patterns of activation in the RAm region.
Social vocalizations were associated with broad activation of neurons throughout the region, while squeaks were associated with a much smaller area. A few neurons were activated by both types, but not many.
The finding in mouse models contributes to understanding how the human brain organizes vocalization, Tschida said, including insight into how neuron degeneration in conditions such as Parkinson’s and Huntington’s diseases alters brain mechanisms and muscle coordination, diminishing speech and communication.
“Longer term, we hope that our work will help us to understand the neural basis for these impairments,” she said.
Aditya Rawal ’27, Zizhan (Jessica) Zhou ’28 and Asmita Mittal ’26 contributed to this research, which was supported by the National Institutes of Health.
Read the story in the Cornell Chronicle.
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