Origins of the Auditory Brainstem Response in Mice Using Source Localization of Topographic Multichannel EEG.

The auditory brainstem response (ABR) is a critical tool for assessing auditory brainstem function in biomedical mouse models. Remarkably, despite its importance, the origins of ABR waves specific to mice remain poorly identified. Here, we used EEG source reconstruction to reevaluate the mouse-specific ABR origins. We recorded the topography of ABRs using high-density EEG from the skull of adult mice of either sex combined with parallel multielectrode recordings in the auditory cortex. Individual ABR waves showed a series of distinct spatial topographies across the skull. Wave I' was strongly lateralized, supporting its auditory nerve origin. Waves II/III were also lateralized but had a more frontal distribution, supporting an origin in the cochlear nucleus and olivary complex. A distinct shift in wave IV topography showed focused activity directly above the inferior colliculus (IC). Source localization with beamforming confirmed the origin of wave IV and V in the IC. In addition, the slow IC wave, P0, temporally overlapped with responses in the auditory cortex. We identify ABR wave IV as an IC marker differentiating olivary complex and cochlear nucleus, as well as thalamic and cortical contributions to the ABR. This improves the specificity of the mouse ABR as a non-invasive tool in biomedical mouse models.Significance Statement Mice are an important model in auditory neuroscience, central to the development of gene therapy for hearing restoration or studying the age-related effects of hearing loss. For this, the auditory brainstem response (ABR) is an invaluable tool to assess not only auditory thresholds, but also auditory brainstem integrity. However, despite its widespread use, only a single study to date has addressed the ABR origins specifically in mice, which has never been independently validated. Here, we provide an updated account of the origins of ABR waves specific to mice using modern innovative methodology and place them in comparative context of ABR sources across species. These results improve the ABR as an important tool for mouse models in auditory neuroscience.