Multi-scale mapping along the auditory hierarchy using high-resolution functional UltraSound in the awake ferret
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.
Reviewing Editor
- Andrew J King, University of Oxford, United Kingdom
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.
Version history
- Received: January 13, 2018
- Accepted: June 16, 2018
- Accepted Manuscript published: June 28, 2018 (version 1)
- 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.
Metrics
-
- 2,470
- views
-
- 376
- downloads
-
- 47
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Neuroscience
Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons toward the prefrontal cortex and shape behaviour. We demonstrate in mice (Mus musculus) that dopamine axons reach the cortex through a transient gradient of Netrin-1-expressing cells – disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters; Phodopus sungorus) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner – delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.
-
- Neuroscience
Acetylcholine is released in visual cortex by axonal projections from the basal forebrain. The signals conveyed by these projections and their computational significance are still unclear. Using two-photon calcium imaging in behaving mice, we show that basal forebrain cholinergic axons in the mouse visual cortex provide a binary locomotion state signal. In these axons, we found no evidence of responses to visual stimuli or visuomotor prediction errors. While optogenetic activation of cholinergic axons in visual cortex in isolation did not drive local neuronal activity, when paired with visuomotor stimuli, it resulted in layer-specific increases of neuronal activity. Responses in layer 5 neurons to both top-down and bottom-up inputs were increased in amplitude and decreased in latency, whereas those in layer 2/3 neurons remained unchanged. Using opto- and chemogenetic manipulations of cholinergic activity, we found acetylcholine to underlie the locomotion-associated decorrelation of activity between neurons in both layer 2/3 and layer 5. Our results suggest that acetylcholine augments the responsiveness of layer 5 neurons to inputs from outside of the local network, possibly enabling faster switching between internal representations during locomotion.