Skip to main content
Log in

Measuring Optokinetic Reflex and Vestibulo-Ocular Reflex in Unilateral Vestibular Organ Damage Model of Zebrafish

  • Original Article
  • Published:
Journal of the Association for Research in Otolaryngology Aims and scope Submit manuscript

Abstract

One-sided vestibular disorders are common in clinical practice; however, their models have not been fully established. We investigated the effect of unilateral or bilateral deficits in the vestibular organs on the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) of zebrafish using in-house equipment. For physical dislodgement of the otoliths in the utricles of zebrafish larvae, one or both utricles were separated from the surrounding tissue using glass capillaries. The video data from VOR and OKR tests with the larvae was collected and processed using digital signal processing techniques such as fast Fourier transform and low-pass filters. The results showed that unilateral and bilateral damage to the vestibular system significantly reduced VOR and OKR. In contrast, no significant difference was observed between unilateral and bilateral damage. This study confirmed that VOR and OKR were significantly reduced in zebrafish with unilateral and bilateral vestibular damage. Follow-up studies on unilateral vestibular disorders can be conducted using this tool.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Availability of Data and Materials

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Strupp M, Dlugaiczyk J, Ertl-Wagner BB, Rujescu D, Westhofen M, Dieterich M (2020) Vestibular disorders Dtsch Arztebl Int 117:300–310. https://doi.org/10.3238/arztebl.2020.0300

    Article  PubMed  Google Scholar 

  2. Aleman M (2022) Vestibular disease. Vet Clin North Am Equine Pract 38:397–407. https://doi.org/10.1016/j.cveq.2022.05.008

    Article  PubMed  Google Scholar 

  3. Gottlob I (2000) Nystagmus. Curr Opin Ophthalmol 11:330–335. https://doi.org/10.1097/00055735-200010000-00007

    Article  CAS  PubMed  Google Scholar 

  4. Dieterich M, Brandt T (1995) Vestibulo-ocular reflex. Curr Opin Neurol 8:83–88. https://doi.org/10.1097/00019052-199502000-00014

    Article  CAS  PubMed  Google Scholar 

  5. Barr CC, Schultheis LW, Robinson DA (1976) Voluntary, non-visual control of the human vestibulo-ocular reflex. Acta Otolaryngol 81:365–375. https://doi.org/10.3109/00016487609107490

    Article  CAS  PubMed  Google Scholar 

  6. Halmagyi GM, Chen L, MacDougall HG, Weber KP, McGarvie LA, Curthoys IS (2017) The video head impulse test. Front Neurol 8:258. https://doi.org/10.3389/fneur.2017.00258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Soussi-Yanicostas N (2022) Zebrafish as a model for neurological disorders. Int J Mol Sci 23. https://doi.org/10.3390/ijms23084321

  8. Nicolson T (2017) The genetics of hair-cell function in zebrafish. J Neurogenet 31:102–112. https://doi.org/10.1080/01677063.2017.1342246

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ehrlich DE, Schoppik D (2017) Control of movement initiation underlies the development of balance. Curr Biol 27:334–344. https://doi.org/10.1016/j.cub.2016.12.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Han E, Ho OhK, Park S, Chan Rah Y, Park HC, Koun S, Choi J (2020) Analysis of behavioral changes in zebrafish (Danio rerio) larvae caused by aminoglycoside-induced damage to the lateral line and muscles. Neurotoxicology 78:134–142. https://doi.org/10.1016/j.neuro.2020.03.005

    Article  CAS  PubMed  Google Scholar 

  11. Han E, Lee DH, Park S, Rah YC, Park HC, Choi JW, Choi J (2022) Noise-induced hearing loss in zebrafish model: characterization of tonotopy and sex-based differences. Hear Res 418:108485. https://doi.org/10.1016/j.heares.2022.108485

    Article  PubMed  Google Scholar 

  12. Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S, Jang S, Haggarty SJ, Kokel D, Rubin LL, Peterson RT, Schier AF (2010) Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science 327:348–351. https://doi.org/10.1126/science.1183090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Furutani-Seiki M, Jiang YJ, Brand M, Heisenberg CP, Houart C, Beuchle D, van Eeden FJ, Granato M, Haffter P, Hammerschmidt M, Kane DA, Kelsh RN, Mullins MC, Odenthal J, Nüsslein-Volhard C (1996) Neural degeneration mutants in the zebrafish, Danio rerio. Development 123:229–239. https://doi.org/10.1242/dev.123.1.229

    Article  CAS  PubMed  Google Scholar 

  14. Hong SJ, Im GJ, Chang J, Chae SW, Lee SH, Kwon SY, Jung HH, Chung AY, Park HC, Choi J (2013) Protective effects of edaravone against cisplatin-induced hair cell damage in zebrafish. Int J Pediatr Otorhinolaryngol 77:1025–1031. https://doi.org/10.1016/j.ijporl.2013.04.003

    Article  PubMed  Google Scholar 

  15. Choi J, Im GJ, Chang J, Chae SW, Lee SH, Kwon SY, Chung AY, Park HC, Jung HH (2013) Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory cell line and in zebrafish. J Appl Toxicol 33:125–133. https://doi.org/10.1002/jat.1729

    Article  CAS  PubMed  Google Scholar 

  16. Han E, Choi YJ, Park S, Rah YC, Park H-C, Lee SH, Choi J (2024) A comprehensive characterizations of zebrafish rheotactic behaviors and its application to otoprotective drug screening. Expert Systems with Applications 237:121496. https://doi.org/10.1016/j.eswa.2023.121496

  17. Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C, Muffato M, Collins JE, Humphray S, McLaren K, Matthews L, McLaren S, Sealy I, Caccamo M, Churcher C, Scott C, Barrett JC, Koch R, Rauch GJ, White S, Chow W, Kilian B, Quintais LT, Guerra-Assunção JA, Zhou Y, Gu Y, Yen J, Vogel JH, Eyre T, Redmond S, Banerjee R, Chi J, Fu B, Langley E, Maguire SF, Laird GK, Lloyd D, Kenyon E, Donaldson S, Sehra H, Almeida-King J, Loveland J, Trevanion S, Jones M, Quail M, Willey D, Hunt A, Burton J, Sims S, McLay K, Plumb B, Davis J, Clee C, Oliver K, Clark R, Riddle C, Elliot D, Threadgold G, Harden G, Ware D, Begum S, Mortimore B, Kerry G, Heath P, Phillimore B, Tracey A, Corby N, Dunn M, Johnson C, Wood J, Clark S, Pelan S, Griffiths G, Smith M, Glithero R, Howden P, Barker N, Lloyd C, Stevens C, Harley J, Holt K, Panagiotidis G, Lovell J, Beasley H, Henderson C, Gordon D, Auger K, Wright D, Collins J, Raisen C, Dyer L, Leung K, Robertson L, Ambridge K, Leongamornlert D, McGuire S, Gilderthorp R, Griffiths C, Manthravadi D, Nichol S, Barker G, Whitehead S, Kay M, Brown J, Murnane C, Gray E, Humphries M, Sycamore N, Barker D, Saunders D, Wallis J, Babbage A, Hammond S, Mashreghi-Mohammadi M, Barr L, Martin S, Wray P, Ellington A, Matthews N, Ellwood M, Woodmansey R, Clark G, Cooper J, Tromans A, Grafham D, Skuce C, Pandian R, Andrews R, Harrison E, Kimberley A, Garnett J, Fosker N, Hall R, Garner P, Kelly D, Bird C, Palmer S, Gehring I, Berger A, Dooley CM, Ersan-Ürün Z, Eser C, Geiger H, Geisler M, Karotki L, Kirn A, Konantz J, Konantz M, Oberländer M, Rudolph-Geiger S, Teucke M, Lanz C, Raddatz G, Osoegawa K, Zhu B, Rapp A, Widaa S, Langford C, Yang F, Schuster SC, Carter NP, Harrow J, Ning Z, Herrero J, Searle SM, Enright A, Geisler R, Plasterk RH, Lee C, Westerfield M, de Jong PJ, Zon LI, Postlethwait JH, Nüsslein-Volhard C, Hubbard TJ, Roest Crollius H, Rogers J, Stemple DL (2013) The zebrafish reference genome sequence and its relationship to the human genome. Nature 496:498–503. https://doi.org/10.1038/nature12111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sun P, Zhang Y, Zhao F, Wu JP, Pun SH, Peng C, Du M, Vai MI, Liu D, Chen F (2018) An assay for systematically quantifying the vestibulo-ocular reflex to assess vestibular function in zebrafish larvae. Front Cell Neurosci 12:257. https://doi.org/10.3389/fncel.2018.00257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Graham SL, Klistorner A (2017) Afferent visual pathways in multiple sclerosis: a review. Clin Exp Ophthalmol 45:62–72. https://doi.org/10.1111/ceo.12751

    Article  PubMed  Google Scholar 

  20. Burn DJ, Lees AJ (2002) Progressive supranuclear palsy: where are we now? Lancet Neurol 1:359–369. https://doi.org/10.1016/s1474-4422(02)00161-8

    Article  PubMed  Google Scholar 

  21. Vargas-Alvarez A, Ninchritz-Becerra E, Goiburu M, Betances F, Rey-Martinez J, Altuna X (2021) Clinical prevalence of enhanced vestibulo-ocular reflex responses on video head impulse test. Otol Neurotol 42:e1160–e1169. https://doi.org/10.1097/mao.0000000000003171

    Article  PubMed  Google Scholar 

  22. Scheetz SD, Shao E, Zhou Y, Cario CL, Bai Q, Burton EA (2018) An open-source method to analyze optokinetic reflex responses in larval zebrafish. J Neurosci Methods 293:329–337. https://doi.org/10.1016/j.jneumeth.2017.10.012

    Article  PubMed  Google Scholar 

  23. Mo W, Chen F, Nechiporuk A, Nicolson T (2010) Quantification of vestibular-induced eye movements in zebrafish larvae. BMC Neurosci 11:110. https://doi.org/10.1186/1471-2202-11-110

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mueller KP, Schnaedelbach OD, Russig HD, Neuhauss SC (2011) VisioTracker, an innovative automated approach to oculomotor analysis. J Vis Exp. https://doi.org/10.3791/3556

    Article  PubMed  PubMed Central  Google Scholar 

  25. Bianco IH, Ma LH, Schoppik D, Robson DN, Orger MB, Beck JC, Li JM, Schier AF, Engert F, Baker R (2012) The tangential nucleus controls a gravito-inertial vestibulo-ocular reflex. Curr Biol 22:1285–1295. https://doi.org/10.1016/j.cub.2012.05.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Roelofs CO (1954) Optokinetic nystagmus. Doc Ophthalmol 7–8:579–650. https://doi.org/10.1007/bf00238148

    Article  PubMed  Google Scholar 

  27. Izawa Y, Suzuki H (2020) Suppressive control of optokinetic and vestibular nystagmus by the primate frontal eye field. J Neurophysiol 124:691–702. https://doi.org/10.1152/jn.00015.2020

    Article  CAS  PubMed  Google Scholar 

  28. Mueller KP, Neuhauss SC (2010) Quantitative measurements of the optokinetic response in adult fish. J Neurosci Methods 186:29–34. https://doi.org/10.1016/j.jneumeth.2009.10.020

    Article  PubMed  Google Scholar 

  29. Beck JC, Gilland E, Tank DW, Baker R (2004) Quantifying the ontogeny of optokinetic and vestibuloocular behaviors in zebrafish, medaka, and goldfish. J Neurophysiol 92:3546–3561. https://doi.org/10.1152/jn.00311.2004

    Article  PubMed  Google Scholar 

  30. Brockerhoff SE, Hurley JB, Janssen-Bienhold U, Neuhauss SC, Driever W, Dowling JE (1995) A behavioral screen for isolating zebrafish mutants with visual system defects. Proc Natl Acad Sci U S A 92:10545–10549. https://doi.org/10.1073/pnas.92.23.10545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Easter SS Jr, Nicola GN (1997) The development of eye movements in the zebrafish (Danio rerio). Dev Psychobiol 31:267–276. https://doi.org/10.1002/(sici)1098-2302(199712)31:4%3c267::aid-dev4%3e3.0.co;2-p

    Article  PubMed  Google Scholar 

  32. Rinner O, Rick JM, Neuhauss SC (2005) Contrast sensitivity, spatial and temporal tuning of the larval zebrafish optokinetic response. Invest Ophthalmol Vis Sci 46:137–142. https://doi.org/10.1167/iovs.04-0682

    Article  PubMed  Google Scholar 

  33. Shao E, Scheetz SD, Xie W, Burton EA (2018) Modulation of the zebrafish optokinetic reflex by pharmacologic agents targeting GABA(A) receptors. Neurosci Lett 671:33–37. https://doi.org/10.1016/j.neulet.2018.01.055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jeong SH, Kim HJ, Kim JS (2013) Vestibular neuritis. Semin Neurol 33:185–194. https://doi.org/10.1055/s-0033-1354598

    Article  PubMed  Google Scholar 

  35. Wright T (2015) Menière’s disease. BMJ Clin Evid 2015

  36. Riley BB, Moorman SJ (2000) Development of utricular otoliths, but not saccular otoliths, is necessary for vestibular function and survival in zebrafish. J Neurobiol 43:329–337. https://doi.org/10.1002/1097-4695(20000615)43:4%3c329::aid-neu2%3e3.0.co;2-h

    Article  CAS  PubMed  Google Scholar 

  37. Roeser T, Baier H (2003) Visuomotor behaviors in larval zebrafish after GFP-guided laser ablation of the optic tectum. J Neurosci 23:3726–3734. https://doi.org/10.1523/jneurosci.23-09-03726.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Virtanen P, Gommers R, Oliphant TE, Haberland M, Reddy T, Cournapeau D, Burovski E, Peterson P, Weckesser W, Bright J, van der Walt SJ, Brett M, Wilson J, Millman KJ, Mayorov N, Nelson ARJ, Jones E, Kern R, Larson E, Carey CJ, Polat İ, Feng Y, Moore EW, VanderPlas J, Laxalde D, Perktold J, Cimrman R, Henriksen I, Quintero EA, Harris CR, Archibald AM, Ribeiro AH, Pedregosa F, van Mulbregt P, Vijaykumar A, Bardelli AP, Rothberg A, Hilboll A, Kloeckner A, Scopatz A, Lee A, Rokem A, Woods CN, Fulton C, Masson C, Häggström C, Fitzgerald C, Nicholson DA, Hagen DR, Pasechnik DV, Olivetti E, Martin E, Wieser E, Silva F, Lenders F, Wilhelm F, Young G, Price GA, Ingold G-L, Allen GE, Lee GR, Audren H, Probst I, Dietrich JP, Silterra J, Webber JT, Slavič J, Nothman J, Buchner J, Kulick J, Schönberger JL, de Miranda Cardoso JV, Reimer J, Harrington J, Rodríguez JLC, Nunez-Iglesias J, Kuczynski J, Tritz K, Thoma M, Newville M, Kümmerer M, Bolingbroke M, Tartre M, Pak M, Smith NJ, Nowaczyk N, Shebanov N, Pavlyk O, Brodtkorb PA, Lee P, McGibbon RT, Feldbauer R, Lewis S, Tygier S, Sievert S, Vigna S, Peterson S, More S, Pudlik T, Oshima T, Pingel TJ, Robitaille TP, Spura T, Jones TR, Cera T, Leslie T, Zito T, Krauss T, Upadhyay U, Halchenko YO, Vázquez-Baeza Y, SciPy C (2020) SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat Methods 17:261–272. https://doi.org/10.1038/s41592-019-0686-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wuyts FL, Furman J, Vanspauwen R, Van de Heyning P (2007) Vestibular function testing. Curr Opin Neurol 20:19–24. https://doi.org/10.1097/WCO.0b013e3280140808

    Article  PubMed  Google Scholar 

  40. Chen CC, Bockisch CJ, Bertolini G, Olasagasti I, Neuhauss SC, Weber KP, Straumann D, Ying-Yu Huang M (2014) Velocity storage mechanism in zebrafish larvae. J Physiol 592:203–214. https://doi.org/10.1113/jphysiol.2013.258640

    Article  CAS  PubMed  Google Scholar 

  41. Domarecka E, Skarzynska M, Szczepek AJ, Hatzopoulos S (2020) Use of zebrafish larvae lateral line to study protection against cisplatin-induced ototoxicity: a scoping review. Int J Immunopathol Pharmacol 34:2058738420959554. https://doi.org/10.1177/2058738420959554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yao Q, DeSmidt AA, Tekin M, Liu X, Lu Z (2016) Hearing assessment in zebrafish during the first week postfertilization. Zebrafish 13:79–86. https://doi.org/10.1089/zeb.2015.1166

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lambert FM, Beck JC, Baker R, Straka H (2008) Semicircular canal size determines the developmental onset of angular vestibuloocular reflexes in larval Xenopus. J Neurosci 28:8086–8095. https://doi.org/10.1523/jneurosci.1288-08.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Liu Z, Hildebrand DGC, Morgan JL, Jia Y, Slimmon N, Bagnall MW (2022) Organization of the gravity-sensing system in zebrafish. Nat Commun 13:5060. https://doi.org/10.1038/s41467-022-32824-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Baeza-Loya S, Raible DW (2023) Vestibular physiology and function in zebrafish. Front Cell Dev Biol 11:1172933. https://doi.org/10.3389/fcell.2023.1172933

    Article  PubMed  PubMed Central  Google Scholar 

  46. Songer JE, Eatock RA (2013) Tuning and timing in mammalian type I hair cells and calyceal synapses. J Neurosci 33:3706–3724. https://doi.org/10.1523/jneurosci.4067-12.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research was supported by Ansan-Si hidden champion fostering and supporting project funded by Ansan city, a Korea University Grant, and Basic Science Research Program through the National Research Foundation of Korea (NRF; 2022R1I1A2072826).

Author information

Authors and Affiliations

Authors

Contributions

Kang Hyeon Lim: conceptualization, methodology, and writing of the original draft. Hong Ki Kim: conceptualization, methodology, and writing of the original draft. Saemi Park: investigation and methodology. Eunjung Han: investigation and methodology. Insik Song: investigation. Hee Soo Yoon: investigation. Jaeyoung Kim: investigation. Yunkyoung Lee: investigation. Yong Hun Jang: investigation. Yoon Chan Rah: investigation. Sang Hyun Lee: supervision, writing, review, and editing. June Choi: supervision, writing, review, and editing.

Corresponding authors

Correspondence to Sang Hyun Lee or June Choi.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (TIF 3389 KB)

Supplementary file2 (TIF 735 KB)

Supplementary file3 (M4V 770 KB)

Supplementary file4 (M4V 193 KB)

Supplementary file5 (M4V 492 KB)

Supplementary file6 (M4V 398 KB)

Supplementary file7 (M4V 1430 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lim, K.H., Kim, H.K., Park, S. et al. Measuring Optokinetic Reflex and Vestibulo-Ocular Reflex in Unilateral Vestibular Organ Damage Model of Zebrafish. JARO 25, 167–177 (2024). https://doi.org/10.1007/s10162-024-00936-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10162-024-00936-3

Keywords

Navigation