Straka MM, Schmitz S, Lim HH. Response features across the auditory midbrain reveal an organization consistent with a dual lemniscal pathway. J Neurophysiol 112: 981-998, 2014. First published May 14, 2014 doi:10.1152/jn.00008.2014.-The central auditory system has traditionally been divided into lemniscal and nonlemniscal pathways leading from the midbrain through the thalamus to the cortex. This view has served as an organizing principle for studying, modeling, and understanding the encoding of sound within the brain. However, there is evidence that the lemniscal pathway could be further divided into at least two subpathways, each potentially coding for sound in different ways. We investigated whether such an interpretation is supported by the spatial distribution of response features in the central nucleus of the inferior colliculus (ICC), the part of the auditory midbrain assigned to the lemniscal pathway. We recorded responses to pure tone stimuli in the ICC of ketamine-xylazineanesthetized guinea pigs and used three-dimensional brain reconstruction techniques to map the location of the recording sites. Compared with neurons in caudal-and-medial regions within an isofrequency lamina of the ICC, neurons in rostral-and-lateral regions responded with shorter first-spike latencies with less spiking jitter, shorter durations of spiking responses, a higher proportion of spikes occurring near the onset of the stimulus, lower thresholds, and larger local field potentials with shorter latencies. Further analysis revealed two distinct clusters of response features located in either the caudal-and-medial or the rostral-and-lateral parts of the isofrequency laminae of the ICC. Thus we report substantial differences in coding properties in two regions of the ICC that are consistent with the hypothesis that the lemniscal pathway is made up of at least two distinct subpathways from the midbrain up to the cortex. functional organization; inferior colliculus; lemniscal; medial geniculate; auditory cortex THE ASCENDING AUDITORY PATHWAY has traditionally been separated into two pathways, the lemniscal "core" pathway and the nonlemniscal pathway (Andersen et al. 1980;Ehret and Romand 1997;Rauschecker and Romanski 2011;Rouiller 1997). The lemniscal pathway includes neurons in the central nucleus of the inferior colliculus (ICC), the ventral division of the medial geniculate body (MGV), and core auditory cortex regions (ACC). Neurons within the lemniscal pathway are tonotopically organized and primarily code for auditory information. Within the ICC and MGV, the tonotopicity derives from an arrangement of isofrequency laminae, where each lamina is a two-dimensional sheet formed by the dendritic arbors of neurons that respond optimally to similar "best frequencies" (Cetas et al. 2001;Imig and Morel 1985;Malmierca et al. 1993;Winer and Schreiner 2005). In contrast, neurons within the nonlemniscal pathway include regions outside of ICC, MGV, and ACC, have poor or no tonotopic organization, code for multimodal information, and are tho...