Modulation of sensory representations in the auditory cortex by callosal inputs

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ProjectAbstract Interhemispheric (callosal) connections between the right and left auditory cortex are suggested to participate in sound localization and speech processing. Furthermore, pathophysiology of auditory callosal projections is proposed to underlie language deficits and auditory hallucinations associated with brain disease. Despite the potential importance of cortical callosal projections in auditory processing, the functional properties of interhemispheric connections are not well understood. Here, we use optogenetic, electrophysiological and imaging approaches in awake, head-fixed mice to determine how callosal projections contribute to sensory coding in primary auditory cortex (A1). Initial anatomical and physiological experiments in brain slices will determine the layer and cell type specificity of callosal inputs. Next, acute and reversible optogenetic silencing of the left auditory cortex combined with linear silicon probe recordings in A1 of the right cortex in awake, head fixed mice will establish how one cortex influences tone-evoked responses in the other. Finally, we will use in vivo two- photon calcium imaging to determine the tonotopic organization of callosal projections and whether it is similar to the tonotopic gradient of target regions. Completion of this work will lend insight into the function of the interhemispheric callosal pathway in the auditory system and will shed light on the mechanisms it uses to modulate sensory representations. A deeper understanding of this pathway will inform the diagnosis and treatment of patients with communication disorders, where the callosum is impacted, in diseases such as multiple sclerosis, schizophrenia, and autism. Hypothesis: Callosal inputs modulate auditory sensory representations in a tonotopic, layer and cell type specific manner. Aim 1. Determine the anatomical distribution of callosal projections and their impact on local circuits in slices of primary auditory cortex. Aim 2. Determine the role of callosal input in primary auditory cortex in awake mice. Aim 3. Define the frequency response properties and tonotopic organization of axonal boutons originating from callosal projections in awake mice using two-photon calcium imaging.