Tuesday, May 7, 2024
5/7/2024
Project Summary The ability to perceive and respond to vocalizations across behavioral contexts is key for survival, but the mechanisms for how the brain derives meaning from acoustic features to drive appropriate behavioral responses remain unknown. I will test the overall hypothesis that top-down control of feed-forward auditory circuits via cortical projection neurons is critical for recognition of social calls and routing of sensory information to circuits driving behavior. In the mentored (K99) phase, I will take advantage of an ethological mouse behavior studied extensively in my postdoctoral lab, in which parentally-experienced mice search for lost pups in response to a specific type of vocalization. Experienced moms are experts at this behavior, but it can also be learned by virgins, and learning is correlated with plasticity in the left auditory cortex in females. Pup retrieval involves a complex sequence of actions, and auditory cues may be required during specific epochs. I will build upon my pilot data finding that cortical projection neurons are necessary for retrieval, and that exposure to pup calls drives sustained activity in a distinct projection in experienced females. Aim 1 (K99) uses imaging and multi-area ensemble recordings to ask how inter-area dynamics in recurrent auditory circuits change during pup calls compared to non-vocal sounds with similar temporal structures, with the hypothesis that network activity is elevated specifically during vocalizations to facilitate brain state modulation or communication with sensorimotor circuits over time scales relevant for behavior. Synaptic mechanisms driving this persistent activity will be examined with in vivo whole-cell recordings. Aim 2 (K99) will test which projection neurons are required for retrieval and over what behavioral time scales. Animals vocalize in multiple situations to communicate distinct meanings – for example, male calls to communicate aggression or courtship – and the brain must make sense of these calls, using acoustic features as well as non-auditory context cues to distinguish between meanings. In the independent phase (R00), Aim 3 asks whether calls are processed with neural ensembles and inter-area dynamics that are generalized across categories or distinct for specific behavioral outcomes. Additionally, the relevance of different social calls can change depending on an animal’s internal state. Aim 4 (R00) investigates whether neural ensemble representations of male calls change in female mice as sexual receptivity varies, measuring activity in cortical ensembles tracked over weeks of experience. In the mentored phase I will complete a training plan designed to strengthen the experimental and computational skills needed for my research program as an independent investigator, and to build the professional skills needed for success as a faculty member, taking advantage of resources and expertise available from the mentor, advisory committee and broader environment at NYU.
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