4-dimensional functional profiling in the convulsant-treated larval zebrafish brain
dc.contributor.author | Winter, MJ | |
dc.contributor.author | Windell, D | |
dc.contributor.author | Metz, J | |
dc.contributor.author | Matthews, P | |
dc.contributor.author | Pinion, J | |
dc.contributor.author | Brown, JT | |
dc.contributor.author | Hetheridge, MJ | |
dc.contributor.author | Ball, JS | |
dc.contributor.author | Owen, SF | |
dc.contributor.author | Redfern, WS | |
dc.contributor.author | Moger, J | |
dc.contributor.author | Randall, AD | |
dc.contributor.author | Tyler, CR | |
dc.date.accessioned | 2017-09-01T11:27:09Z | |
dc.date.issued | 2017-07-26 | |
dc.description.abstract | Functional neuroimaging, using genetically-encoded Ca(2+) sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders. | en_GB |
dc.description.sponsorship | This work was funded by the Biological and Biotechnology Research Council (CASE studentship BB/L502510/1, with AstraZeneca Safety Health and Environment), and by the University of Exeter and AstraZeneca. | en_GB |
dc.identifier.citation | Vol. 7, article 6581 | en_GB |
dc.identifier.doi | 10.1038/s41598-017-06646-6 | |
dc.identifier.uri | http://hdl.handle.net/10871/29159 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Nature | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/28747660 | en_GB |
dc.rights | © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | en_GB |
dc.title | 4-dimensional functional profiling in the convulsant-treated larval zebrafish brain | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2017-09-01T11:27:09Z | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the final version of the article. Available from Springer Nature via the DOI in this record. | en_GB |
dc.identifier.journal | Scientific Reports | en_GB |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's licence is described as © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.