The ability to extract meaning from sounds, even when degraded, is critical for normal hearing. A key strategy employed by the auditory system during acoustically-challenging situations is the use of contextual cues to disambiguate cluttered signals. Importantly, many patients with language-related disorders, such as aphasia, autism and dyslexia, have difficulties harnessing such contextual cues. The neural mechanisms by which high-level information can be used to shape lower-level sensory processing are not yet known. A potential substrate for this type of processing is the massive top-down projection system emanating from virtually every level of the auditory system. In this project, we will provide a functional characterization of one of the largest of these projections: the auditory corticocollicular system. The corticocollicular system can rapidly and profoundly change the tuning of neurons in the inferior colliculus, but key aspects about its organization are not known. We hypothesize that this system comprises at least two functionally distinct sub- systems; one from cortical layer 5 and another from cortical layer 6. Using the mouse model, the cortical distribution of layer 5 and 6 neurons that project to small regions of the inferior colliculus willbe reconstructed and compared. Our early data suggest that input from layer 6 emanates from a more widespread area than layer 5 and tends to predominate in the non-primary parts of the auditory cortex. In addition, we will combine in vivo transcranial flavoprotein autofluoresence imaging with quantitative neuronal reconstructions to compare the projection patterns of layer 5 vs. layer 6 cortical projections to the inferior colliculus. Finally, using a novel corticocolliculr brain slice preparation and laser photostimulation, we will compare the synaptic properties of layer 5 and 6 corticocollicular synapses. Successful completion of this project will provide the first circuit-level characterization of this important pathway and will lay the groundwork for a greater understanding of how top-down modulatory systems break down during disorders of communication.
Many disorders of hearing and language involve the inability to use contextual cues to navigate noisy or cluttered environments and it is not currently known how the brain uses these cues. We will investigate one major brain pathway that is potentially involved in this process: the corticocollicular pathway. By using a combination of modern approaches, we will characterize this pathway to shed light on how it may become dysfunctional in disease states such as aphasia, autism and dyslexia.
