Summary: Researchers have identified a specific node in the brain of mice that regulates vocalizations in response to social situations. If a similar location could be found in the human brain, researchers say it could potentially lead to new insight into social dysfunctions associated with autism and depression.
Source: Scripps Research Institute
What’s the difference between a giggle and a belly laugh? Or a yelp and an all-out scream? In many species, including humans, the volume and duration of a verbal sound conveys as much information as the noise itself.
A group of scientists, led by Scripps Research, has discovered a node in the brains of male mice that modulates the sounds they make in social situations. This discovery, published in Nature, could help identify similar locations in the human brain, and potentially lead to a better understanding of social disorders such as autism or depression.
“Identifying this node gives us signatures of what to look for when human behavior goes awry,” says Lisa Stowers, PhD, a neuroscientist and professor at Scripps Research who led the study. “It’s giving us clues to how information is organized in the brain, and how different features of information can be separated out in different brain regions.”
As part of their courtship behavior, male mice produce “songs.” These complicated whistles, which are too high for the human ear to detect, are louder and longer when the female mouse is nearby or when her scent is stronger. The researchers identified a specific type of neuron in a part of the hypothalamus called the lateral preoptic area that controls the emotional regulation of these sounds.
“The hypothalamus and the rest of the limbic system control body functions such as hunger, thirst and temperature regulation, as well as the basic features of emotional behavior like sex and fear,” Stowers says. “It is fitting that the emotional aspect of these social noises are generated in this region of the brain.”
By directly stimulating the right nodes from these neurons, the scientists could trigger the whole array of noises that go into a mouse song. Varying the level of stimulation allowed them to control how enthusiastic those sounds were.
When the researchers blocked these nodes, male mice encountering a female would attempt to court her in silence. (Female mice responded by kicking the males and running away.) If the researchers bypassed these nodes and activated the next node downstream, the male mice only made long, loud noises.
“They’re basically just shouting,” Stowers says. “By finding these neurons, it’s telling us that this part of the brain is doing this emotional scaling and persistence. If you take that away, then you lose all of that affect, all of that emotional range, and the ability to have effective social communication.”
Most research on noise production in the brain has focused on language development, Stowers says. But the sounds that even an infant can make–a giggle, a cry, a scream–don’t have to be learned and are just as vital for communication. Identifying how the brain decides on these responses is the first step to understanding where things can go wrong in social behavioral disorders such as autism and depression.
“We are starting to get a detailed look at where in the brain different types of computations are being made,” Stowers says. “Now that we know that this simple behavior is regulated in the hypothalamus, we can study whether others behaviors are also using similar circuits and if so, perhaps find a common mechanism–and drug target–for when emotions are not generated appropriately.”
The study, “Flexible scaling and persistence of social vocal communication,” was authored by Jingyi Chen, Jeffrey Markowitz, Varoth Lilascharoen, Sandra Taylor, Pete Sheurpukdi, Jason Keller, Jennifer Jensen, Byung Kook Lim, Sandeep Robert Datta and Lisa Stowers.
Funding: Funding was provided by the Dorris Neuroscience and Skaggs Scholarships, the Anandamahidol Foundation Fellowship, Career Award at the Scientific Interface from BWF and the National Institutes of Health (R01NS097772, R01DA049787, R01NS108439).
Flexible scaling and persistence of social vocal communication
Innate vocal sounds such as laughing, screaming or crying convey one’s feelings to others. In many species, including humans, scaling the amplitude and duration of vocalizations is essential for effective social communication. In mice, female scent triggers male mice to emit innate courtship ultrasonic vocalizations (USVs). However, whether mice flexibly scale their vocalizations and how neural circuits are structured to generate flexibility remain largely unknown.
Here we identify mouse neurons from the lateral preoptic area (LPOA) that express oestrogen receptor 1 (LPOAESR1 neurons) and, when activated, elicit the complete repertoire of USV syllables emitted during natural courtship. Neural anatomy and functional data reveal a two-step, di-synaptic circuit motif in which primary long-range inhibitory LPOAESR1 neurons relieve a clamp of local periaqueductal grey (PAG) inhibition, enabling excitatory PAG USV-gating neurons to trigger vocalizations.
We find that social context shapes a wide range of USV amplitudes and bout durations. This variability is absent when PAG neurons are stimulated directly; PAG-evoked vocalizations are time-locked to neural activity and stereotypically loud. By contrast, increasing the activity of LPOAESR1 neurons scales the amplitude of vocalizations, and delaying the recovery of the inhibition clamp prolongs USV bouts.
Thus, the LPOA disinhibition motif contributes to flexible loudness and the duration and persistence of bouts, which are key aspects of effective vocal social communication.