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The Journal of Neuroscience, September 27, 2006, 26(39):9873-9880; doi:10.1523/JNEUROSCI.2886-06.2006

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Development/Plasticity/Repair
Oculomotor Instabilities in Zebrafish Mutant belladonna: A Behavioral Model for Congenital Nystagmus Caused by Axonal Misrouting

Ying-Yu Huang,^1,2 Oliver Rinner,² Patrik Hedinger,¹ Shih-Chii Liu,³ and Stephan C. F. Neuhauss^1,2

¹Institute of Zoology, ²Swiss Federal Institute of Technology (ETH) Zurich, Department of Biology, and Brain Research Institute, and ³Institute of Neuroinformatics and ETH Zurich, University of Zurich, CH-8057 Zurich, Switzerland

Correspondence should be addressed to Stephan C. F. Neuhauss, Institute of Zoology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Email: stephan.neuhauss{at}zool.unizh.ch

A large fraction of homozygous zebrafish mutant belladonna (bel) larvae display a reversed optokinetic response (OKR) that correlates with failure of the retinal ganglion cells to cross the midline and form the optic chiasm. Some of these achiasmatic mutants display strong spontaneous eye oscillations (SOs) in the absence of motion in the surround. The presentation of a stationary grating was necessary and sufficient to evoke SO. Both OKR reversal and SO depend on vision and are contrast sensitive.

We built a quantitative model derived from bel fwd (forward) eye behaviors. To mimic the achiasmatic condition, we reversed the sign of the retinal slip velocity in the model, thereby successfully reproducing both reversed OKR and SO. On the basis of the OKR data, and with the support of the quantitative model, we hypothesize that the reversed OKR and the SO can be completely attributed to RGC misrouting. The strong resemblance between the SO and congenital nystagmus (CN) seen in humans with defective retinotectal projections implies that CN, of so far unknown etiology, may be directly caused by a projection defect.

Key words: zebrafish; reversed optokinetic response; congenital nystagmus; oculomotor instability; achiasmatic; retinal ganglion cell axons; axonal misrouting; quantitative model; behavioral genetics

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Received March 16, 2006; accepted Aug. 4, 2006.

Correspondence should be addressed to Stephan C. F. Neuhauss, Institute of Zoology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Email: stephan.neuhauss{at}zool.unizh.ch

eLetters:

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An oculomotor phenotype in question.

James C Beck

J. Neurosci. Online, 21 Mar 2007 [Full text]

Re: An oculomotor phenotype in question.

Stephan C.F. Neuhauss, et al.

J. Neurosci. Online, 7 May 2007 [Full text]

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