1. Neuroscience
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Multi-scale mapping along the auditory hierarchy using high-resolution functional UltraSound in the awake ferret

  1. Célian Bimbard
  2. Charlie Demene
  3. Constantin Girard
  4. Susanne Radtke-Schuller
  5. Shihab Shamma
  6. Mickael Tanter  Is a corresponding author
  7. Yves Boubenec  Is a corresponding author
  1. CNRS UMR 8248, École Normale Supérieure, PSL Research University, France
  2. ESPCI ParisTech, PSL Research University, France
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Cite this article as: eLife 2018;7:e35028 doi: 10.7554/eLife.35028

Abstract

A major challenge in neuroscience is to longitudinally monitor whole brain activity across multiple spatial scales in the same animal. Functional UltraSound (fUS) is an emerging technology that offers images of cerebral blood volume over large brain portions. Here we show for the first time its capability to resolve the functional organization of sensory systems at multiple scales in awake animals, both within small structures by precisely mapping and differentiating sensory responses, and between structures by elucidating the connectivity scheme of top-down projections. We demonstrate that fUS provides stable (over days), yet rapid, highly-resolved 3D tonotopic maps in the auditory pathway of awake ferrets, thus revealing its unprecedented functional resolution (100/300µm). This was performed in four different brain regions, including very small (1-2mm3 size), deeply situated subcortical (8mm deep) and previously undescribed structures in the ferret. Furthermore, we used fUS to map long-distance projections from frontal cortex, a key source of sensory response modulation, to auditory cortex.

Article and author information

Author details

  1. Célian Bimbard

    Laboratoire des Systèmes Perceptifs, CNRS UMR 8248, École Normale Supérieure, PSL Research University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Charlie Demene

    Institut Langevin, ESPCI ParisTech, PSL Research University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Constantin Girard

    Laboratoire des Systèmes Perceptifs, CNRS UMR 8248, École Normale Supérieure, PSL Research University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Susanne Radtke-Schuller

    Laboratoire des Systèmes Perceptifs, CNRS UMR 8248, École Normale Supérieure, PSL Research University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Shihab Shamma

    Laboratoire des Systèmes Perceptifs, CNRS UMR 8248, École Normale Supérieure, PSL Research University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Mickael Tanter

    Institut Langevin, ESPCI ParisTech, PSL Research University, Paris, France
    For correspondence
    mickael.tanter@espci.fr
    Competing interests
    The authors declare that no competing interests exist.
  7. Yves Boubenec

    Laboratoire des Systèmes Perceptifs, CNRS UMR 8248, École Normale Supérieure, PSL Research University, Paris, France
    For correspondence
    boubenec@ens.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0106-6947

Funding

European Commission (339244-FUSIMAGINE)

  • Charlie Demene
  • Mickael Tanter

European Commission (ADG_20110406-ADAM)

  • Célian Bimbard
  • Constantin Girard
  • Susanne Radtke-Schuller
  • Shihab Shamma
  • Yves Boubenec

Agence Nationale de la Recherche (ANR-10-LABX-0087 IEC)

  • Célian Bimbard
  • Constantin Girard
  • Shihab Shamma
  • Yves Boubenec

Agence Nationale de la Recherche (ANR-10-IDEX-0001-02 PSL*)

  • Célian Bimbard
  • Charlie Demene
  • Constantin Girard
  • Susanne Radtke-Schuller
  • Shihab Shamma
  • Mickael Tanter
  • Yves Boubenec

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments were approved by the French Ministry of Agriculture (protocol authorization: 01236.02) and strictly comply with the European directives on the protection of animals used for scientific purposes (2010/63/EU). All surgery was performed under anaesthesia (isoflurane 1%), and every effort was made to minimize suffering.

Reviewing Editor

  1. Andrew J King, University of Oxford, United Kingdom

Publication history

  1. Received: January 13, 2018
  2. Accepted: June 16, 2018
  3. Accepted Manuscript published: June 28, 2018 (version 1)
  4. Version of Record published: July 10, 2018 (version 2)

Copyright

© 2018, Bimbard et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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    Edoardo Bistaffa et al.
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    Background: Fatal Familial Insomnia (FFI) is a genetic prion disease caused by the D178N mutation in the prion protein gene (PRNP) in coupling phase with methionine at PRNP 129. In 2017, we have shown that the olfactory mucosa (OM) collected from FFI patients contained traces of PrPSc detectable by Protein Misfolding Cyclic Amplification (PMCA).

    Methods In this work, we have challenged PMCA generated products obtained from OM and brain homogenate of FFI patients in BvPrP-Tg407 transgenic mice expressing the bank vole prion protein to test their ability to induce prion pathology.

    Results: All inoculated mice developed mild spongiform changes, astroglial activation and PrPSc deposition mainly affecting the thalamus. However, their neuropathological alterations were different from those found in the brain of BvPrP-Tg407 mice injected with raw FFI brain homogenate.

    Conclusions: Although with some experimental constraints, we show that PrPSc present in OM of FFI patients is potentially infectious.

    Funding: This work was supported in part by the Italian Ministry of Health (GR-2013-02355724 and Ricerca Corrente), MJFF, ALZ, Alzheimer's Research UK and the Weston Brain Institute (BAND2015), and Euronanomed III (Speedy) to FM; by the Spanish Ministerio de Economía y Competitividad [grant AGL2016-78054-R (AEI/FEDER, UE)] to J.M.T. and J.C.E.; A.M.-M. was supported by a fellowship from the INIA (FPI-SGIT-2015-02).

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    Sensory-guided limb control relies on communication across sensorimotor loops. For active touch with the hand, the longest loop is the transcortical continuation of ascending pathways, particularly the lemnisco-cortical and corticocortical pathways carrying tactile signals via the cuneate nucleus, ventral posterior lateral (VPL) thalamus, and primary somatosensory (S1) and motor (M1) cortices to reach corticospinal neurons and influence descending activity. We characterized excitatory connectivity along this pathway in the mouse. In the lemnisco-cortical leg, disynaptic cuneate→VPL→S1 connections excited mainly layer (L) 4 neurons. In the corticocortical leg, S1→M1 connections from L2/3 and L5A neurons mainly excited downstream L2/3 neurons, which excite corticospinal neurons. The findings provide a detailed new wiring diagram for the hand/forelimb-related transcortical circuit, delineating a basic but complex set of cell-type-specific feedforward excitatory connections that selectively and extensively engage diverse intratelencephalic projection neurons, thereby polysynaptically linking subcortical somatosensory input to cortical motor output to spinal cord.