Thalamic input to auditory cortex is locally heterogeneous but globally tonotopic.

Topographic representation of the receptor surface is a fundamental feature of sensory cortical organization. This is imparted by the thalamus, which relays information from the periphery to the cortex. To better understand the rules governing thalamocortical connectivity and the origin of cortical maps, we used in vivo two-photon calcium imaging to characterize the properties of thalamic axons innervating different layers of mouse auditory cortex. Although tonotopically organized at a global level, we found that the frequency selectivity of individual thalamocortical axons is surprisingly heterogeneous, even in layers 3b/4 of the primary cortical areas, where the thalamic input is dominated by the lemniscal projection. We also show that thalamocortical input to layer 1 includes collaterals from axons innervating layers 3b/4 and is largely in register with the main input targeting those layers. Such locally varied thalamocortical projections may be useful in enabling rapid contextual modulation of cortical frequency representations.

Functional Microarchitecture of the Mouse Dorsal Inferior Colliculus Revealed through In Vivo Two-Photon Calcium Imaging.

The inferior colliculus (IC) is an obligatory relay for ascending auditory inputs from the brainstem and receives descending input from the auditory cortex. The IC comprises a central nucleus (CNIC), surrounded by several shell regions, but the internal organization of this midbrain nucleus remains incompletely understood. We used two-photon calcium imaging to study the functional microarchitecture of both neurons in the mouse dorsal IC and corticocollicular axons that terminate there. In contrast to previous electrophysiological studies, our approach revealed a clear functional distinction between the CNIC and the dorsal cortex of the IC (DCIC), suggesting that the mouse midbrain is more similar to that of other mammals than previously thought. We found that the DCIC comprises a thin sheet of neurons, sometimes extending barely 100 µm below the pial surface. The sound frequency representation in the DCIC approximated the mouse's full hearing range, whereas dorsal CNIC neurons almost exclusively preferred low frequencies. The response properties of neurons in these two regions were otherwise surprisingly similar, and the frequency tuning of DCIC neurons was only slightly broader than that of CNIC neurons. In several animals, frequency gradients were observed in the DCIC, and a comparable tonotopic arrangement was observed across the boutons of the corticocollicular axons, which form a dense mesh beneath the dorsal surface of the IC. Nevertheless, acoustically responsive corticocollicular boutons were sparse, produced unreliable responses, and were more broadly tuned than DCIC neurons, suggesting that they have a largely modulatory rather than driving influence on auditory midbrain neurons. SIGNIFICANCE STATEMENT: Due to its genetic tractability, the mouse is fast becoming the most popular animal model for sensory neuroscience. Nevertheless, many aspects of its neural architecture are still poorly understood. Here, we image the dorsal auditory midbrain and its inputs from the cortex, revealing a hitherto hidden level of organization and paving the way for the direct observation of corticocollicular interactions. We show that a precise functional organization exists in the mouse auditory midbrain, which has been missed by previous, more macroscopic approaches. The fine-scale distribution of sound-frequency tuning suggests that the mouse midbrain is more similar to that of other mammals than previously thought and contrasts with the more heterogeneous organization reported in imaging studies of auditory cortex.