The significance of nominally non-responsive neural dynamics in auditory perception and behavior

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The auditory system is often challenged with the task of assigning behavioral meaning to sounds: the cry of an infant immediately commands your attention, a fire alarm signals the need for a hasty departure, and the familiar sound of your cell phone causes an early exit from a meeting. How does the brain accomplish this seemingly effortless feat? A network of regions in the brain are implicated in the act of auditory perception, but even regions thought to be primarily concerned with the representation of sounds have cells that seem unmoved by the behaviorally-relevant acoustic inputs. These “nominally non-responsive cells” are highly prevalent, underexplored, and may provide key insights into how the brain accomplishes auditory-related learning and contextualizes audition. For example, there is emerging evidence that these cells are important for generating flexible behaviors. Developing a systems-level understanding of these widely observed but rarely analyzed neurons is essential for relating auditory-related behavior to neural activity in the auditory pathway and may yield critical insights into rehabilitation strategies for cochlear-implant (CI) users as CI stimulation can result in highly variable cortical activation. This proposal will investigate how nominally non-responsive cells emerge and evolve over auditory learning to construct flexible neuronal representations in a central auditory pathway. I aim to dissect the local and long- range circuit dynamics that modulate nominally non-responsive activity during learning and discover how these dynamics gate auditory learning and perception. This proposal leverages cutting-edge electrophysiological recordings in behaving rats, optogenetic manipulation, and computational tools to address the following aim: Determine how auditory circuits are modulated in a central auditory axis during learning (Aim 2). The results from this work will provide critical insights into how animals process sounds with behavioral significance and remain flexible in behaviorally challenging environments. Clarification of the specific role each auditory station plays in generating adaptive behaviors will have implications for improving diagnosis and treatment of hearing deficits caused by disease or injury as well as auditory prosthetic devices to enhance auditory perception. In these cases, we lack clinically proven measures for whether the activity of highly variable neurons is normal, which makes judging the efficacy of treatments at the neural level challenging. Determining the relevance and utility of this large population of highly variable cells to auditory learning and perception is the goal of this proposal.