In Vivo Dissection of Auditory Corticofugal Circuits

Massachusetts Eye And Ear Infirmary, Boston MA

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Abstract

? DESCRIPTION (provided by applicant): Understanding how neural circuits process sensory information in order to drive behavior is a fundamental question in modern neuroscience. At early stages of the auditory pathway, function can often be inferred from patterns of connectivity and intrinsic electrical properties. This problem becomes far more difficult at higher levels, largely because neural responses no longer faithfully represent the features of the incoming sensory stimuli. Instead, responses can be readily modified by a host of non-sensory factors including attention, learning, and arousal. Thus, in order to understand the function of such circuits, it becomes crucial not only to isolate the functional identity of the cell types recorded from, but also to characterize how they contribute to acoustic signal processing while animals are engaged in purposeful behaviors. Recently, two cortical projection systems have been implicated as playing distinct roles in active listening behaviors. It has been suggested that subcortical feedback from auditory cortex to the inferior colliculus is critical in updating behaviorally relevant sensory representations in the midbrain. In contrast, the projection from auditory cortex to the striatum has been shown to encode the transformation between stimulus and action. However, in order to address the question of precisely how these projections are able to drive behavior, it is necessary to characterize their sensory tuning properties to understand exactly what information they are capable of carrying. Recent technical developments now make it possible to isolate specific neuron classes in vivo and document their specific contributions to auditory processing and sound-guided behavior. To this end, we will leverage these new techniques to identify and characterize the response properties of cortico-collicular and cortico-striatal neurons. We will then record from these neurons during task-engagement and employ optogenetic strategies to probe the role that these projections play in guiding auditory behaviors. Findings from the proposed studies will elucidate cortical contributions to behavior and will lay the foundation for a better understanding of the causes of neurological and behavioral disorders.