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singing mice

Cold Spring Harbor Laboratory neuroscientist Arkarup Banerjee is using singing mice, like the one shown here, to understand how our brains control timing and communication. Photo by Christopher Auger-Dominguez

By Daniel Dunaief

Animals don’t have clocks, telling them when and for how long to run on a treadmill, to eat whatever they catch or to call to each other from the tops of trees or the bottom of a forest.

Arkarup Banerjee

The Alston’s singing mouse, which lives in Costa Rica, has a distinctive call that people can hear and that, more importantly, conveys meaning to other members of the species.

Using equipment to monitor neurons when a mouse offers songs of different length, Cold Spring Harbor Assistant Professor Arkarup Banerjee showed that these unusual rodents exhibit a form a temporal scaling that is akin to stretching or relaxing a rubber band. This scaling suggests that their brains are bending their processing of time to produce songs of different lengths.

“People have shown this kind of time stretching phenomenon in monkeys,” said Banerjee. It was unexpected and surprising that the same algorithm was used in the rodent motor cortex to control the flexibility of a motor pattern and action during vocalization.

Using recordings of neuronal activity over many weeks, Banerjee focused on a part of the mouse brain called the orofacial motor cortex (or OMC). He searched for differences in songs with particular durations and tempo.

Banerjee had set up a system in which he played back the recordings of Alston’s singing mice to his test subjects, who then responded to those songs. Mice generally respond with songs that are variable durations compared to when they sing alone.

These mice can adjust duration and tempo of these 10-second long songs while engaged in social communication.

People “do that all the time,” said Banerjee. “We change the volume of how loud we are speaking and we can change the tempo.”

The mice showed some vocal flexibility similar to other animals, including people.

These mice are singing the same song, with varying rhythms over shorter or longer periods of time. It is as if the same person were to sing “Happy Birthday” in 10 seconds or in 15 seconds.

Banerjee would like to know what is it in the mouse’s brain that allows for such flexibility. He had previously shown that the motor cortex is involved in vocal behavior, which meant he knew of at least one region where he could look for clues about how these rodents were controlling the flexibility of their songs.

By tracking the firing pattern of neurons in the OMC, he was able to relate neural activity to what the mice were doing in real time.

Neural activity expands or contracts in time, almost as if time is running faster or slower. These animals are experiencing relative time when it comes to producing their songs as they change their songs through a wide range of durations.

Pre-song activity

Even before an animal sings, Banerjee speculates its brain could be preparing for the sounds it’s going to make, much as we think of the words we want to say in a conversation or our response to a question before we move our mouths to reply or type on a keyboard to respond.

Songs also track with intruder status. An animal in a home cage sings a shorter song than an animal brought into a new cage.

Vocalizations may scale with social rank, which might help attract mates or serve other social purposes.

Females in the lab, which presumably reflect similar trends in the wild, tend to prefer the male that produces a longer song with a higher tempo, which could reflect their physical fitness and their position in the social hierarchy, according to research from Steve Phelps, Professor at the University of Texas at Austin in the Department of Integrative Biology.


While it’s a long way from the research he’s conducting to any potential human application, Banerjee could envision ways for these studies to shed light on communication processes and disorders.

The motor cortex in humans and primate is a larger region. Problems in these areas, from strokes or injuries, can result in aphasia, or the inability to articulate words properly. Banerjee plans to look at stroke models to see if the Alston’s singing mouse might provide clues about potential diagnostic or therapeutic clues.

“There are ways we can use this particular system to study cognitive deficits that show up” during articulation deficits such as those caused by strokes, said Banerjee.  While he said scientists know the parts list of the brain regions involved in speaking, they don’t yet know how they all interact.

“If we did, we’d have a much better chance of knowing where it fails,” Banerjee  explained. A challenge along this long process is learning how to generalize any finding in mice to humans. While difficult, this is not an impossible extrapolation, he suggested.

An effective model

Banerjee built a model prior to these experiments to connect neural activity with behavior.

“We had an extremely clear hypothesis about what should happen in the neural domain,” he said. “It was pretty gratifying to see that neurons change the way we predicted given the modeling.”

When the paper first came out about eight months ago in the scientific preprint bioRxiv, it received considerable attention from Banerjee’s colleagues working in similar fields. He went to India to give three talks and gave a recent talk at Emory University.

Outside of the lab, Banerjee and his wife Sanchari Ghosh, who live in Mineola, are enjoying watching the growth and development of their son Ahir, who was born a year and a half ago.

“It’s fascinating as a neuroscientist to watch his development and to see how a tiny human being learns about the world,” Banerjee said.

As for his work with this compelling mouse, Banerjee credited Phelps and his post doctoral advisor at New York University, Michael Long for doing important work on this mouse and for encouraging him to pursue research with this species. Long is a co-corresponding author on the paper. “It’s very gratifying to see that the expectation of what we can do with this species is starting to get fulfilled,” said Banerjee. “We can do these interesting and complex experiments and learn something about vocal interactions. I’m excited about the future.”



The Cinema Arts Centre, 423 Park Ave., Huntington continues its Science on Screen series with a mind-expanding exploration of the mysteries of language and communication, featuring a lecture and Q&A with neuroscientist Arkarup Banerjee, of Cold Spring Harbor Laboratory, and a rare big-screen showing of Denis Villeneuve’s profound 2016 drama ARRIVAL on Tuesday, March 26 at 7 p.m..

Dr. Banerjee’s work explores the theme of decoding messages and touches on the fundamental assumptions of reality which are unpacked in the film. Discover how every species and culture’s unique symbols and codes shape our understanding of the world around us, and uncover the intriguing ways in which our brains navigate the limits and possibilities of language.

Tickets are $16, $10 members. To purchase in advance, visit www.cinemaartscentre.org. 

Arkarup Banerjee. Photo from CSHL

By Daniel Dunaief

Arkarup Banerjee is coming back home to Cold Spring Harbor Laboratory. This time, instead of working on the olfactory system, the way he did in Associate Professor Dinu Florin Albeanu’s lab from 2010 to 2016, he is studying vocalizations in the Alston’s singing mouse, a Central American rodent.

Banerjee rejoined Cold Spring Harbor Laboratory in November after almost four years of post-doctoral work at NYU Langone Medical Center. He hopes to use the study of the way these mice react to songs and the way they formulate them to understand how signals from the brain lead to vocalizations.

Singing Mouse

“The reason I decided to come back to Cold Spring Harbor Laboratory is not just because I did my PhD here,” said Banerjee, who is an assistant professor. “Neuroscience [at the lab] is amazing. I have fantastic colleagues. I expect to have lots of collaborations.” CSHL is one of his “top choices” in part because of the ability to interact with other researchers and to attend meetings and courses, he said.

To hear Albeanu tell it, CSHL’s colleagues appreciate the skill and determination Banerjee, whom Albeanu described as a “rare catch,” brings to the site.

“There was pretty much unanimous excitement about his vision for his research,” Albeanu said. “Pretty much everyone was in agreement that [hiring Banerjee] is a must.”

Fundamentally, Banerjee is interested in understanding how the brain computes information. In his new lab at CSHL, he wanted to study the natural behaviors that animals produce without having to teach them anything.

“That’s why my fascination arose in singing mice,” he said. “Nobody has to train them to vocalize.” He hopes to understand the neural circuits in the context of a natural behavior.

In the longer term, Banerjee is interested in contributing to the field of human communication. While numerous other creatures, such as birds, interact with each other vocally, singing from trees as they establish territorial dominance and soliciting mates through their songs, mice, which have cerebral cortexes, have brain architecture that is more similar to humans.

The Alston’s singing mice, which is found in the cloud forests of Costa Rica and Panama, is also different from numerous other species of mice. Many rodents produce vocalizations in the ultrasonic range. These animals can hear calls that are outside the range of human capacity to pick up such sounds.

The singing mice Banerjee is studying produces a stereotyped song that is audible to people. “These mice seem to specialize in this behavior,” he said. In neuroscience, scientists seek animals that are specialists with the hope that understanding that species will reveal how they work, he said.

Audible communications are important for male mice in attracting mates and in guarding their locations against other males. These lower-frequency sounds travel across greater distances.

Specifically, Banerjee would like to know the anatomical differences between the brains of typical rodents and the singing mice. He plans to probe “what kind of changes does it require for a new behavior to emerge during evolution.”

The songs have some value to the males who sing them. Females prefer males who sing more notes per unit time in a 10-second period.

In his experiments, Banerjee has demonstrated that the conventional view about one of the differences between humans and other vocalizing animals may not be accurate. Scientists had previously believed that other animals didn’t use their cortex to produce songs. Banerjee, however, showed that the motor cortex was important for vocal behaviors. Specifically, animals with temporarily inactivated cortexes could not participate in vocal interactions.

As a long term goal, Banerjee is also interested in the genetic sequence that makes the development of any anatomical or behavioral feature different in these singing mice. By using the gene editing tool CRISPR, which CSHL scientists employ regularly, Banerjee hopes to find specific genetic regions that lead to these unique behaviors.

Arkarup Banerjee with Honggoo Chae, a post-doctoral fellow at CSHL, from a Society of Neuroscience Meeting in 2018.

An extension of this research could apply to people with various communication challenges. Through studies of mice with different genetic sequences, Banerjee and other researchers can try to find genes that are necessary for more typical vocalizations. By figuring out the genetic differences, the CSHL scientist may one day discover what researchers could do to minimize these differences.

A resident of Mineola, Banerjee lives with his wife Sanchari Ghosh, who works at Cold Spring Harbor Laboratory press for the preprint service bioRxiv. The couple, who met in India, spend considerable time discussing their shared interest in neuroscience. Banerjee said his wife is a “much better writer” than he and has helped edit his manuscripts.

Banerjee is passionate about teaching and hopes he has a chance to educate more students once the pandemic recedes. Outside the lab, Banerjee shares an important quality with the mice he studies: he sings. He trained as a vocalist when he was growing up in India, and listens to a range of music.

Albeanu, who was teaching a course in Bangalore, India in 2009 when he met Banerjee, said it is a “pleasure to listen to [Banerjee] singing.”

Albeanu recalls how Banerjee stood out for many reasons when he first met him, including developing a way to modify a microscope.

As for his work, Banerjee hopes to understand behaviors like vocalizations from numerous perspectives. “We can seek explanations for all of these levels,” he said.

A neuroscientist by training, Banerjee would like to determine the connection between neural circuitry and the behavior it produces. “The understanding would be incomplete if I didn’t understand why this behavior is being generated.”