Multi-scale mapping along the auditory hierarchy using high-resolution functional UltraSound in the awake ferret
- CNRS UMR 8248, École Normale Supérieure, PSL Research University, France
- ESPCI ParisTech, PSL Research University, France
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.
Data availability
The data that support the findings of this study can be found at https://lsp.dec.ens.fr/en/research/supporting-materials-848. The full raw imaging files are >20Tb and are therefore available on request to the corresponding author.
Article and author information
Author details
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.
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.
Metrics
-
- 2,605
- views
-
- 398
- downloads
-
- 55
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Multi-scale mapping along the auditory hierarchy using high-resolution functional UltraSound in the awake ferret
eLife 7:e35028.
https://doi.org/10.7554/eLife.35028
Further reading
-
- Neuroscience
By influencing calcium homeostasis, local protein synthesis and the endoplasmic reticulum, a small protein called Rab10 emerges as a crucial cytoplasmic regulator of neuropeptide secretion.
-
- Neuroscience
Millions of Americans suffering from Opioid Use Disorders face a high risk of fatal overdose due to opioid-induced respiratory depression (OIRD). Fentanyl, a powerful synthetic opioid, is a major contributor to the rising rates of overdose deaths. Reversing fentanyl overdoses has proved challenging due to its high potency and the rapid onset of OIRD. We assessed the contributions of central and peripheral mu opioid receptors (MORs) in mediating fentanyl-induced physiological responses. The peripherally restricted MOR antagonist naloxone methiodide (NLXM) both prevented and reversed OIRD to a degree comparable to that of naloxone (NLX), indicating substantial involvement of peripheral MORs to OIRD. Interestingly, NLXM-mediated OIRD reversal did not produce aversive behaviors observed after NLX. We show that neurons in the nucleus of the solitary tract (nTS), the first central synapse of peripheral afferents, exhibit a biphasic activity profile following fentanyl exposure. NLXM pretreatment attenuates this activity, suggesting that these responses are mediated by peripheral MORs. Together, these findings establish a critical role for peripheral MORs, including ascending inputs to the nTS, as sites of dysfunction during OIRD. Furthermore, selective peripheral MOR antagonism could be a promising therapeutic strategy for managing OIRD by sparing CNS-driven acute opioid-associated withdrawal and aversion observed after NLX.
