title: Functional Microarchitecture of the Mouse Dorsal Inferior Colliculus Revealed through In Vivo Two-Photon Calcium Imaging.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom, and Centre for Neural Circuits and Behaviour, University of Oxford, Oxford OX1 3SR, United Kingdom.
authors.forename: Oliver
authors.identifier: http://orcid.org/0000-0001-7924-6043
authors.initials: O
authors.lastname: Barnstedt
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom, and.
authors.forename: Peter
authors.initials: P
authors.lastname: Keating
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom, and.
authors.forename: Yves
authors.identifier: http://orcid.org/0000-0001-5756-661X
authors.initials: Y
authors.lastname: Weissenberger
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom, and andrew.king@dpag.ox.ac.uk johannes.dahmen@dpag.ox.ac.uk.
authors.forename: Andrew J
authors.identifier: http://orcid.org/0000-0001-5180-7179
authors.initials: AJ
authors.lastname: King
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom, and andrew.king@dpag.ox.ac.uk johannes.dahmen@dpag.ox.ac.uk.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Dahmen
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000502:physiology*; D001931:Brain Mapping; D002118:Calcium / Q000378:metabolism*; D059907:Functional Neuroimaging / Q000379:methods*; D007245:Inferior Colliculi / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000502:physiology*
chemical_list: D002118:Calcium
keywords: GCaMP6; bouton; corticocollicular projection; inferior colliculus; tonotopic; two-photon calcium imaging