Circuit dynamics of predictive vocal suppression in auditory cortex

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Project summary During vocalization, the nervous system must dissociate vocal feedback from other sounds. To make this distinction, vocal motor-related signals are harnessed to selectively suppress responses of auditory neurons to predictable acoustic features of vocal feedback. This predictive suppression enhances the detection of sounds that occur simultaneously with vocal feedback and also facilitates the detection of vocal errors, a process important to vocal learning. In contrast, dysfunctional suppression is thought to give rise to auditory hallucinations in disorders like schizophrenia. The prominence of predictive vocal suppression in the auditory cortex has been most thoroughly demonstrated with noninvasive recordings in speaking humans and extracellular recordings from pyramidal neurons in vocalizing monkeys. However, the cellular determinants of predictive vocal suppression are unknown because the auditory cortex of monkeys and humans is not readily amenable to advanced genetic methods useful for circuit interrogation. While our group previously found that mouse auditory cortex was suppressed during vocalization, these recordings were conducted during courtship, a state that also features locomotion, arousal, and olfactory stimulation, all of which broadly suppress pyramidal neuron activity. I have developed a novel social interaction paradigm in which I can monitor vocalizations, locomotion, and arousal while conducting multiphoton imaging the activity of pyramidal neurons and interneurons in the mouse auditory cortex. I have combined this paradigm with sound presentations to test the excitability of auditory cortical neurons during vocal and non-vocal social interactions. In Aim 1, I will use this approach to measure suppression related to vocalization, locomotion, and arousal during social interactions to test the hypothesis that vocalization corresponds with specific suppression of pyramidal neurons that respond to vocal feedback and activation of certain interneurons, while non-vocal facets of courtship suppress a broader population of neurons. In Aim 2.1, I will image from the auditory cortex while systematically distorting vocal feedback with air enriched with gradations of helium to test the hypothesis that vocal suppression is predictive of vocal feedback. In Aim 2.2, I will test the hypothesis that vocal suppression relies on strong activation of interneurons by vocal motor-related signals by imaging from the auditory cortex of vocalizing, congenitally deaf mice. These experiments will test the specificity and predictive power of vocal suppression in the mouse auditory cortex while providing cellular resolution of its underlying mechanisms. Given the similar organization of the human and mouse auditory cortex, my findings will shed light on cortical circuits that influence vocal perception during human speech and whose dysfunction interferes with communication and well-being.