The circuits responsible for vocal communication are one of the most important and least understood in the human brain. This project uses mice to discover evolutionarily conserved mechanisms to represent and interpret vocal communication. Mice have simpler vocalizations, are more amenable to scientific inquiry, and have brain organization homologous to humans. Sensory processing of sounds begins at the ear where a representation of different sound frequencies arises and gets relayed to an area of the brain called the auditory cortex. This area is involved in some of the earliest complex operations needed to recognition vocal sound patterns, but the neural mechanisms remain mysterious. It is believed that one important strategy the brain utilizes to process vocalizations is to assign distinct computational tasks to the left and right auditory cortices, a division of labor called lateralization. Conceptually, this project will exploit this functional lateralization to dissect the neural mechanisms underlying vocalization processing. The instructions to brain functions and ultimately behavior are found in the precise connections neurons make with one another. Therefore, identifying lateralized circuit-motifs in the auditory cortices and linking them to sound processing functions is the foundation of this proposal. Using cutting-edge techniques for high-throughput circuit mapping, functional imaging, and optogenetics, this project will compare the development, connectivity and operations of the left and right auditory cortices. The results and framework of this proposal will be powerful tools to establish how the auditory cortex encodes the communicative significance of sounds. A unique aspect of the educational component of the project is to train students to develop of animations of various topics in Neuroscience to be distributed on various educational sites.
Vocalizations offer unique advantages for survival and social interactions by allowing animals to communicate rapidly over a range of distances, and encode an individual's identity. Accordingly, an animal's brain must perform the challenging tasks of recognizing, categorizing, and assigning communicative importance to sounds in a noisy environment. From humans to mice the auditory cortex performs many of these tasks, but the neural mechanisms are unknown. One strategy believed to be important in processing vocalizations is the division of computational tasks between the left and right auditory cortices (i.e. lateralization). The investigators will exploit lateralization to reveal functional differences between the auditory cortices that may underlie specializations responsible for extracting the valence and meaning of vocalizations. The firing pattern of individual neurons in response to sensory input defines its neural code and is determined by a neuron's precise pattern of synaptic connections. Hence, it is necessary to obtain the connectivity profile of cell types to link coding strategies with functional significance. Using the molecular toolbox available in the mouse the investigators will identify neuronal populations with lateralized activation using the activity marker c-fos, use circuit-mapping techniques in vitro to screen for lateralized circuit-motifs, and determine the contribution of sensory experience in the development of lateralized auditory processing. Circuit-level insights will guide experiments in vivo to establish their functional significance using a combination of electrophysiology and optogenetics. The results will reveal specializations underlying lateralized functions, and provide a short-list of testable neural mechanisms responsible for vocalization processing. In addition to training graduate students and undergraduates, the PI will work with the Biology Animation Assistantship program at CCNY to create and make available animations on topics ranging from synaptic transmission to audition. A Student Assessment of Learning Gains survey will be given to assess the benefit of the assistantship.
