Project Summary/Abstract The sense of hearing contributes significantly to our quality of life. Indeed, the auditory system plays a fundamental role in our awareness of our local environment, communication, and our ability to enjoy music. However, the mechanisms underlying the processing and encoding of sensory information in the brain are not clear. To address this question, we study the properties of neuronal circuits in the auditory cortex, a higher brain region important for sound perception. The long-term objective of our research is to understand how the interplay of different types of excitatory and inhibitory circuits regulate sensory information processing in the brain. The experiments proposed employ optical recording techniques to study the response properties of large ensembles of neurons in auditory cortex. Specific Aim 1 proposes the development of a strategy for chronic, in vivo two-photon recording of activity from identified cell populations in the primary auditory cortex of awake, head-fixed mice. We will use this approach to determine the tuning properties and spatial organization of principal cells in different cortical layers as well as distinct subtypes of inhibitory interneurons. Specific Aim 2 proposes to investigate how sensory representations in adult auditory cortex are shaped by experience. We hypothesize that brief daily experience to sounds causes a long-lasting habituation of cortical principal cell responses mediated by local inhibitory interneurons. Specific Aim 3 proposes to investigate how cortical activity is modulated by sound-guided behavior. We hypothesize that engagement in an auditory task rapidly enhances cortical representations to sounds compared to passive listening. Moreover, this modulation by sound-guided behavior is also due to changes in the activity of local interneurons. Together, these experiments will show that cortical sensory representations are highly flexible and bidirectionally modulated by local inhibitory circuits that regulate the salience of acoustic stimuli.