Cited by 185Vestibular and auditory disordersVisual perception and processing mechanismsMotor Control and Adaptation

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Optogenetic Localization and Genetic Perturbation of Saccade-Generating Neurons in Zebrafish

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Schoonheim, Peter J., Arrenberg, Aristides B., Del Bene, Filippo, Baier, Herwig·2010·The Journal of Neuroscience

DOI 10.1523/jneurosci.5193-09.2010PMC PMC3842466

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Abstract

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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Authors: Schoonheim, P. J., Arrenberg, A. B., Del Bene, F., & Baier, H.
Affiliations: University of California, San Francisco (US)
Corresponding author: Baier, Herwig
ORCID: Arrenberg, Aristides B.
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
DOI: 10.1523/jneurosci.5193-09.2010
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: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
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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Optogenetic Localization and Genetic Perturbation of Saccade-Generating Neurons in Zebrafish

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