PUBLICATION

4-dimensional functional profiling in the convulsant-treated larval zebrafish brain

Authors
Winter, M.J., Windell, D., Metz, J., Matthews, P., Pinion, J., Brown, J.T., Hetheridge, M.J., Ball, J.S., Owen, S.F., Redfern, W.S., Moger, J., Randall, A.D., Tyler, C.R.
ID
ZDB-PUB-170728-4
Date
2017
Source
Scientific Reports   7: 6581 (Journal)
Registered Authors
Tyler, Charles R.
Keywords
Fluorescence imaging, Neural circuits
MeSH Terms
  • Animals
  • Brain/diagnostic imaging*
  • Brain/drug effects*
  • Convulsants/administration & dosage*
  • Functional Neuroimaging/methods*
  • Spatio-Temporal Analysis
  • Zebrafish
PubMed
28747660 Full text @ Sci. Rep.
Abstract
Functional neuroimaging, using genetically-encoded Ca2+ 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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping