The primary goal of my lab is to investigate brain-wide neural circuits for vocal communication. We use the rich vocal behavior of the Alston's singing mice to pursue two complementary questions. First, how does the auditory system interact with the motor system to generate the fast sensorimotor loop required for vocal communication? Second, what are the neural circuit modifications that allow behavioral novelty to emerge during evolution? Using a comparative approach, we investigate brain-wide connectivity and neural circuitry differences between the Alston's singing mouse and other rodent species (for e.g. the lab mouse) that have intermediate degree of vocal behavior. Overall, research in the lab combines cutting-edge neural circuit analysis of a natural behavior with comparative evolutionary analyses across species to gain insight into the function and evolution of neural circuits for vocal communication.

Projects in the lab

Motor Cortical Dynamics during Vocal Production 

(collaboration with Michael Long, NYU and Shaul Druckmann, Stanford University)

 

Social interactions often require behavioral flexibility to coordinate across individuals. For instance, conversations involving intricately entwining speech with minimal delays. Similarly, in the Alston’s singing mouse (Scotinomys teguina), vocal partners can take part in fast and flexible counter-singing in which two animals can coordinate their ~10 s songs with silent gaps of ~500 ms. Recently, we discovered that a cortical locus in the singing mouse, the orofacial motor cortex (OMC), is crucial for coordinated vocal interactions; inactivation of this region abolished counter-singing behavior (Okobi*, Banerjee*, et al., 2019, Banerjee et. al., 2019).). However, the circuit dynamics within the OMC and their impact on vocal production remained unclear.

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Neural circuits for context specific switching of vocalizations 

Lab mice elicit ultrasonic vocalizations (USV) in social contexts, while singing mice produce both USVs and stereotyped advertisement songs. The species-specific USVs are known to be controlled by periaqueductal gray (PAG) and anterior cingulate cortex (ACC). Previous work in the lab has showed that the advertisement songs in singing mice are modulated by orofacial motor cortex (OMC). This current study focuses on understanding the neural circuits underlying these two types of vocalizations. Over the last year, we have built a behavioral rig suitable for high-speed videography to track the 3D poses of freely moving animals. Future analysis of the pose data will not only describe the pose dynamics during vocalizations but also uncover the organization of behavior in singing mice. Currently, we are using optogenetics to test the role of OMC in song initiation and maintenance by transiently perturbing neural activity during different parts of the song. We will perform electrophysiological recordings subsequently to understand the neural circuits of vocal motor control across the two rodent species.

Comparative Connectomics and Transcriptomics in Lab mice and Singing mice.

Despite a close evolutionary relationship, Alston’s singing mice (Scotinomys teguina) and lab mice (Mus Musculus) exhibit extremely divergent vocal behaviors. This behavioral divergence must derive from differences in the underlying biology of neural cell types and/or neural circuits. To test this hypothesis, we are applying technology developed by the Zador lab to determine the neural circuits of vocal behavior in lab and singing mice. We have begun our connectomic comparison in the orofacial motor cortex (OMC), a brain area involved in the singing mouse song proven through electrical, pharmacological, and cooling experiments (Okobi, Banerjee, et al., 2019). We are using both bulk methods (viral tracing followed by whole brain two-photon tomography) and single cell barcoding methods (MAPseq) to characterize the projection patterns of neurons in the OMC of the two species. Our future directions include using single nucleus RNAseq (snRNAseq) and BARseq2 (an in situ sequencing technique that combines gene expression and projection data) to determine differences in cell type and the spatial location of these cells in the OMC of lab and singing mice. We hope to discover the differences in molecular identity, spatial distribution and projection patterns of specific cell-types in the OMC of the two species. Finding transcriptomic and neural circuit differences between lab and singing mice will give insights into the evolution of neural circuits underlying vocal behavior.

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Our Team

1. Clifford Harpole (postdoctoral fellow)   2. Mike Zheng (CSH Graduate student)    3. Emily Isko (CSH Graduate student)

4. Martin Davis (Senior technician)