Tonotopic and non-auditory organization of the mouse dorsal inferior colliculus revealed by two-photon imaging

Abstract

The dorsal (DCIC) and lateral cortices (LCIC) of the inferior colliculus are major targets of the auditory and non-auditory cortical areas, suggesting a role in complex multimodal information processing. However, relatively little is known about their functional organization. We utilized in vivo two-photon Ca2+ imaging in awake mice expressing GCaMP6s in GABAergic or non-GABAergic neurons in the IC to investigate their spatial organization. We found different classes of temporal responses, which we confirmed with simultaneous juxtacellular electrophysiology. Both GABAergic and non-GABAergic neurons showed spatial microheterogeneity in their temporal responses. In contrast, a robust, double rostromedial-caudolateral gradient of frequency tuning was conserved between the two groups, and even among the subclasses. This, together with the existence of a subset of neurons sensitive to spontaneous movements, provides functional evidence for redefining the border between DCIC and LCIC.

Efferent feedback enforces bilateral coupling of spontaneous activity in the developing auditory system

“…A tonotopic organization of isofrequency bands was observed in both control and knockout animals (columns enclosed in vertical dashed rectangles in Figure 5D), with the medial region of the IC preferentially responding to low frequency, while more lateral regions favored higher frequencies. Typical responses consisted of pairs of bands symmetrically located against the tilted anterior-lateral axes (Movie S7), consistent with the known tonotopic-reversal organization in the IC (Wong and Borst, 2019). Interestingly, we observed a significant elevation on the threshold level of the α9/α10 knockout across the frequency spectrum at P14.0 compared to controls ( Figure 5E).…”

“…Our experiments revealed the trajectories of key spatiotemporal features of IC spontaneous activity bands throughout the entire pre-hearing period. We observed characteristic organizational features imbedded in the intrinsic dynamics of spontaneous activity in the pre-hearing IC, including discrete functional clusters (Malmierca et al, 2008) and tonotopic-reversals (Wong and Borst, 2019). The large field-of-view afforded by wide-field imaging and the intact in vivo preparation permits the direct measurement of functional connectivity across ipsilateral and contralateral hemispheres that are millimeters apart.…”

“…Specifically, when the representative seed was in the medial IC (putative future low-frequency region), we observed a single correlation band on each side. When the representative seed moved laterally towards the future mid-or high-frequency region of the IC, we observed dual correlation bands that shifted correspondingly to more lateral regions on each side (see Movie S3), reflecting the known reversal of tonotopic organization in each hemisphere (Wong and Borst, 2019). Symmetrical patterns on the two sides of the IC indicate that coupling of bilateral spontaneous activity is itself tonotopic.…”

“…We resolved functional modules that are consistent with known characteristic organization of the IC solely based on spontaneous activity patterns. Specifically, diffusion map results displayed two mirror-symmetrical domains, matching the tonotopic-reversal structure in the dorsal IC (Wong and Borst, 2019). K-means analysis extracted evolving but discrete functional clusters, which are reminiscent of separate fibro-dendritic laminae and discontinuous stepwise response curves in the IC (Jeffery A.…”

“…The IC contains three major divisions: the central nucleus (CNIC), the lateral cortex (LCIC), and the dorsal cortex (DCIC). Only the dorsal parts of the IC, including DCIC and LCIC, are accessible for calcium imaging (Babola et al, 2018, Wong andBorst, 2019). Consistent with previous reports (Babola et al, 2018, Babola et al, 2020, typical spontaneous calcium transients in the dorsal surface of the IC appear as stationary and discrete events that (1) have a relatively homogeneous intensity profile along their major axis, (2) show confined spread along the future tonotopic axis that is approximately perpendicular to the major axis ( Figures 1C and Supplementary Figure 1B, major axes labeled as magenta arrows), and (3) appear as a single band in the most medial part or dual bands in more lateral parts of the IC (See also Movie S1).…”