Project Summary This renewal application will focus on the striatum. It stems from our recent study of the functional contributions of major corticofugal projections from the auditory cortex (ACx). Anatomically receiving convergent cortical and thalamic inputs, the striatum is believed to play an important role in central auditory processing and perception of sound, as evidenced by its involvement in sound-frequency discrimination related behaviors. However, fundamental questions about how specific auditory information is processed, integrated in the striatum, and transformed into appropriate actions remain not well understood. Since the caudal striatum, or the tail of the striatum (TS), receives the highest intensity of ACx projections among all striatal areas, our initial efforts will be centered on the TS, regarded as the “auditory striatum”, to explore its functional role in auditory processing and related behaviors. This proposal builds upon our recent studies on corticostriatal projections from ACx to TS in processing looming sounds, as well as on the mouse cortico-striatal-thalamic network. More importantly, our pilot results suggest that a midbrain structure adjacent to the MGB, known as the nucleus of the brachium of the inferior colliculus (NB in Allen mouse brain atlas, also named “NBIC” or “BIN” in the literature), provides significant bottom-up auditory signals to TS and influences its auditory processing. By exploiting mouse genetic models and combining a suite of cutting-edge approaches such as cell-type- and pathway-specific viral tracing, our recently established AAV1-based anterograde transsynaptic tagging, in vivo and ex vivo electrophysiology, miniscope calcium imaging, as well as optogenetic manipulations, we will test our central hypothesis that TS contributes to auditory spatial processing by integrating binaural information relayed from a unique ascending midbrain-striatal pathway. The proposed project aims to generate new insights into the functional role of striatum in auditory processing perception. Results from this project may help to advance our understanding of the pathophysiology of auditory processing disorders as well as striatum-related neuropsychiatric disorders.