Cold Spring Harbor Laboratory
Neural Circuits for Flexible Vocal Communication
Circuits of interacting neurons enable us to sense and respond to stimuli, combine them with past experiences, and move our muscles to interact with the world. By mapping, manipulating and measuring activity of various circuit elements, I wish to understand how neural circuits compute, and guide behavior.
To study sensorimotor control, researchers increasingly use rodent models and simple behavioral tasks in which animals learn to associate arbitrary sensory cues with motor responses. Ultimately, however, we would like to understand the sensorimotor transformations in a more naturalistic context. Vocal interactions, such as during a conversation, provides an ideal backdrop to study this question. Humans engaged in conversation, for example, take rapid turns to go back and forth–a feat that most of us tend to perform effortlessly, but which breaks down during neuropsychiatric disorders. How do neural circuits in the brain enable vocal communication, especially in mammals, remains mostly unknown.
Recently, we have discovered that Alston’s singing mouse, a highly vocal rodent from the Cloud forests of Costa Rica, engages in fast and flexible vocal interactions, even under laboratory settings. Singing mice produce a stereotypic sequence of notes strung together in a “song” that can last for about 6 to 16 s. As the name suggests, these rodents sing spontaneous “solo” songs as well as “duets” with another male. The latter is known as counter-singing and resembles the back-and-forth structure of human conversation. These mice are polite enough to take turns to sing! My laboratory, using this novel model system, seeks to pursue two main avenues of research.
Neural circuit function enabling vocal communication: During a conversation, our brain must interpret what we hear and control our vocal response. How does the brain transform these auditory sensations into action? Using quantitative behavioral measurements, in-vivo electrophysiology from both auditory and motor cortex, and projection-specific optogenetic perturbations, we are interrogating the role of this bi-directional auditory-motor connectivity for enabling vocal interactions.
Evolution of neural circuits for vocal communication: Singing mice and lab mice are separated by a ~24 million years of evolution. Despite the fact that the species are roughly same size, and that their brain slices are nearly indistinguishable, there are key behavioral differences. Lab mice produce only short, variable ultrasonic vocalizations (USVs), while S. teguina produce both USVs and human-audible “songs”. Crucially, unlike singing mice, lab mice do not participate in vocal interactions. For complex behaviors, genes must act via neural circuits in the brain. Hence, we ask: what are the neural circuit differences underlying the behavioral divergence between the singing mice and lab mice? By tagging individual neurons with RNA barcodes and sequencing them in brain regions of interest, we are mapping brain-wide projection targets of motor and auditory cortex. This allows single-cell resolution circuit mapping with high-throughput across the two rodent species.
Our research program, at the intersection of systems neuroscience, ecology, and comparative evolution will allow us to decipher the function and evolution of neural circuits underlying flexible vocal communication in mammals.