Current Research
Neural Mechanisms of Vocal Interactions
Using cutting-edge circuit mapping, measurement, and manipulation approaches, we are investigating sensorimotor computations during vocal communication, from sensory evidence accumulation and decision-making to motor planning and production. Recent work has focussed on the motor cortex and the midbrain PAG.
Ecological Function of Vocal Communication​
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Vocal communication involves bi-directional information exchange between sender and receiver. Through quantitative behavioral measurements, we have discovered that dyadic vocal interactions emerge from the interplay between internal states and external auditory inputs, establishing that they follow two fundamental rules: acoustic jamming avoidance with a partner and responding quickly after the partner's song. We are now testing whether these dyadic rules of engagement can explain interactions among larger groups.
Evolution of a Novel Vocalization
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We are investigating the mechanistic basis of vocal innovations at the molecular, cellular and circuit levels. We take a reverse engineering approach: By starting with causally defined circuits, we can trace mechanistic changes from wiring to cell types and ultimately to genetic regulatory elements. Recent work is focussed on ​using DNA barcoded projection mapping to test whether species-specific differences in brain-wide connectivity underlie behavioral divergences between singing mice and laboratory mice.
Ontogeny of a Novel Vocalization​
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Singing mouse produce both a novel specialized vocalization (songs) and the ancestral ultrasonic vocalizations (USVs) ubiquitous among rodents. We study ontogeny to understand how changes in developmental programs may lead to the evolution of a novel vocal behavior.
Selected Techniques
Quantitative Behavioral Measurements
Chronic Electrophysiology
We routinely perform silicon probe recordings from freely behaving singing mice to track the neural representation of sensorimotor variables during vocal behaviors. On the left is the raster plot of an example motor cortex neuron during 29 songs in a given behavioral session. We are currently recording neural activity in the motor cortex and the midbrain PAG.
Viral Tracing and 2-Photon Tomography
Brain-wide projection patterns of motor cortical neurons using AAV based viral tracing imaged by serial two-photon tomography. This allows us to map projections from selected brain regions.
Barcoded Neuroanatomy
Causal Circuit Manipulations
PAIRId behavioral paradigm: Two singing mice interacting in close-range through a perforated barrier producing softer ultrasonic vocalizations (USVs) and louder songs. Using this paradigm, we are able to assign ~90% of all vocalizations to individual mice.
Barcoded neuroanatomy involves uniquely tagging neurons with distinct RNA barcodes. The barcodes are expressed and then actively transported into the axonal processes of each labeled neuron. Target regions identified in bulk tracing are then dissected, and barcodes are extracted and analyzed by high-throughput barcode sequencing. This method's high-throughput and single-cell resolution make it ideally suited to probe quantitative differences in brain-wide projection patterns across species
To go beyond measurement and establish causal contribution of neural circuit elements, we routinely employ viral tools to perform optogenetic and chemogenetic experiments. Most viral tools, already established for small rodents over the last decades, work well in the singing mouse.
