RRC ID 54978
Author Vladimirov N, Wang C, Höckendorf B, Pujala A, Tanimoto M, Mu Y, Yang CT, Wittenbach JD, Freeman J, Preibisch S, Koyama M, Keller PJ, Ahrens MB.
Title Brain-wide circuit interrogation at the cellular level guided by online analysis of neuronal function.
Journal Nat Methods
Abstract Whole-brain imaging allows for comprehensive functional mapping of distributed neural pathways, but neuronal perturbation experiments are usually limited to targeting predefined regions or genetically identifiable cell types. To complement whole-brain measures of activity with brain-wide manipulations for testing causal interactions, we introduce a system that uses measured activity patterns to guide optical perturbations of any subset of neurons in the same fictively behaving larval zebrafish. First, a light-sheet microscope collects whole-brain data that are rapidly analyzed by a distributed computing system to generate functional brain maps. On the basis of these maps, the experimenter can then optically ablate neurons and image activity changes across the brain. We applied this method to characterize contributions of behaviorally tuned populations to the optomotor response. We extended the system to optogenetically stimulate arbitrary subsets of neurons during whole-brain imaging. These open-source methods enable delineating the contributions of neurons to brain-wide circuit dynamics and behavior in individual animals.
Volume 15(12)
Pages 1117-1125
Published 2018-12-1
DOI 10.1038/s41592-018-0221-x
PII 10.1038/s41592-018-0221-x
PMID 30504888
MeSH Animals Behavior, Animal / physiology* Brain / cytology Brain / physiology* Brain Mapping / methods* Larva / physiology* Neural Pathways Neurons / cytology Neurons / physiology* Online Systems* Swimming Zebrafish / physiology*
IF 28.467
Times Cited 10
Zebrafish Tg(vglut2a:loxP-DsRed-loxP-GFP) Tg(gad1b:|R|-GFP)