Resubmission of Functional approach to communication sound processing in mouse auditory cortex

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PROJECT SUMMARY Acoustic communication is critical for normal social interactions in many species, including humans, yet so- cial aspects of communication functions and dysfunctions are often overlooked in studies of how the brain re- sponds to and learns communication sounds. One key brain mechanism concerns the neural plasticity within the auditory cortex to support learning the social meaning of new communication sounds. However, our circuit and cellular level understanding of such plasticity is more often based on studies where a sound's salience is acquired through nonsocial reinforcement procedures, rather than from rewarding social interactions. Hence, there is a gap in our knowledge of the neural principles for communication sound processing and plasticity during more realistic social auditory learning. Our long-term goal is to understand the circuit and cellular mechanisms under- lying the auditory system's encoding of socially-learned sound categories, so that causes underlying deficits in communication processing can be inferred. Our objective here is to uncover whether socially learning a sound category alters higher-order auditory cortical fields' neuronal tuning and tolerance for acoustic variability in that category's sound features. Our central hypothesis is that both Core auditory cortex and secondary auditory cor- tical field A2 are intrinsically tuned to parameters describing complex frequency trajectories of sounds, with neu- rons in a secondary field exhibiting greater tolerance in these parameters. Learning the social meaning of a specific sound category then biases neurons along a feedforward pathway through Core and A2 to become more attuned to the likely parameters of the learned category. We investigate this hypothesis by exploiting a maternal mouse model of ultrasonic communication between pups and adult females. When pup calls become behavior- ally relevant to mothers, neurons in the auditory cortex changes how they respond in ways that were not expected from nonsocial auditory learning paradigms. This proposal addresses the underlying neural mechanisms in two specific aims. First, using extracellular electrophysiology, we will determine how the neural transformation from Core to A2 alters neuronal tuning and tolerance for the acoustic features of the pup call category. Second, using a new socially-reinforced auditory training paradigm, we will determine how calibrated, explicit social experience with a novel sound category modifies the Core to A2 neural transformation. This research's significance lies in its unique ability to bridge the scientific gap between sensory and social/behavioral neuroscience in an animal model in which studies of a high level auditory function (communication) can be conducted from a systems down to a molecular level.