The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Optogenetic Localization and Genetic Perturbation of Saccade-Generating Neurons in Zebrafish
Open accessAbstract
The optokinetic response (OKR) to a visual stimulus moving at constant velocity consists of a series of two alternating components, a slow phase, during which the eyes follow the stimulus, and a quick phase, which resets the eyes to begin a new response cycle. The quick phases of the OKR resemble the saccades observed during free viewing. It is unclear to what extent the premotor circuitry underlying these two types of jerky, conjugate eye movements is conserved among vertebrates. Zebrafish (Danio rerio) larvae, broadly expressing halorhodopsin (NpHR) or channelrhodopsin-2 (ChR2) in most neurons, were used to map the location of neurons involved in this behavior. By blocking activity in localized groups of NpHR-expressing neurons with an optic fiber positioned above the head of the fish and by systematically varying the site of photostimulation, we discovered that activity in a small hindbrain area in rhombomere 5 was necessary for saccades to occur. Unilateral block of activity at this site affected behavior in a direction-specific manner. Inhibition of the right side suppressed rightward saccades of both eyes, while leaving leftward saccades unaffected, and vice versa. Photostimulation of this area in ChR2-transgenic fish was sufficient to trigger saccades that were precisely locked to the light pulses. These extra saccades could be induced both during free viewing and during the OKR, and were distinct in their kinetics from eye movements elicited by stimulating the abducens motor neurons. Zebrafish double indemnity(didy) mutants were identified in a chemical mutagenesis screen based on a defect in sustaining saccades during OKR. Positional cloning, molecular analysis, and electrophysiology revealed that the didy mutation disrupts the voltage-gated sodium channel Scn1lab (Nav1.lb). ChR2 photostimulation of the putative hindbrain saccade generator was able to fully reconstitute saccades in the didy mutant. Our studies demonstrate that an optogenetic approach is useful for targeted loss-of-function and gain-of-function manipulations of neural circuitry underlying eye movements in zebrafish and that the saccade-generating circuit in this species shares many of its properties with that in mammals.
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“The imaged volume includes neurons involved in eye movements16,21,22,28.”
From Predicting modular functions and neural coding of behavior from a synaptic wiring diagram (2024) · cites this paper as [28]
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Metadata
- Authors
- Schoonheim, P. J., Arrenberg, A. B., Del Bene, F., & Baier, H.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Baier, Herwig
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-05-19
- Volume
- 30
- Issue
- 20
- Pages
- 7111-7120
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3842466
- OpenAlex
- W2084811348
- Cited by
- 185
- References
- 49
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 9 · 2023: 11 · 2022: 6 · 2021: 8 · 2020: 18 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 16 · 2015: 12 · 2014: 13 · 2013: 13 · 2012: 11
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Boehringer Ingelheim Stiftung
- National Institutes of Health
- National Eye Institute (R01EY012406)
- National Institute of Neurological Disorders and Stroke (R01NS053358)
- Topics
- Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Keywords
- saccades, optokinetic response, zebrafish, halorhodopsin, channelrhodopsin-2, optogenetics, voltage-gated sodium channels, eye movements, conjugate eye movements, photostimulation
- MeSH terms
- Animals, Bacterial Proteins, Carrier Proteins, Kinetics, Larva, Luminescent Proteins, Microinjections, Mutation, Neurons, Oocytes, Photic Stimulation, Reaction Time, Rhombencephalon, Saccades, Xenopus, Zebrafish, Sodium Channels, Mutagenesis, Site-Directed, Nystagmus, Optokinetic, Halorhodopsins, Zebrafish Proteins, Animals, Genetically Modified
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