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Quantitative Assessment of Anti-Gravity Reflexes to Evaluate Vestibular Dysfunction in Rats

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Abstract

The tail-lift reflex and the air-righting reflex are anti-gravity reflexes in rats that depend on vestibular function. To obtain objective and quantitative measures of performance, we recorded these reflexes with slow-motion video in two experiments. In the first experiment, vestibular dysfunction was elicited by acute exposure to 0 (control), 400, 600, or 1000 mg/kg of 3,3′-iminodipropionitrile (IDPN), which causes dose-dependent hair cell degeneration. In the second, rats were exposed to sub-chronic IDPN in the drinking water for 0 (control), 4, or 8 weeks; this causes reversible or irreversible loss of vestibular function depending on exposure time. In the tail-lift test, we obtained the minimum angle defined during the lift and descent maneuver by the nose, the back of the neck, and the base of the tail. In the air-righting test, we obtained the time to right the head. We also obtained vestibular dysfunction ratings (VDRs) using a previously validated behavioral test battery. Each measure, VDR, tail-lift angle, and air-righting time demonstrated dose-dependent loss of vestibular function after acute IDPN and time-dependent loss of vestibular function after sub-chronic IDPN. All measures showed high correlations between each other, and maximal correlation coefficients were found between VDRs and tail-lift angles. In scanning electron microscopy evaluation of the vestibular sensory epithelia, the utricle and the saccule showed diverse pathological outcomes, suggesting that they have a different role in these reflexes. We conclude that these anti-gravity reflexes provide useful objective and quantitative measures of vestibular function in rats that are open to further development.

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Acknowledgments

The scanning electron microscopy studies were performed at the Scientific and Technological Centers of the University of Barcelona (CCiT-UB). We thank Josep M. Rebled and Eva Parts for technical assistance. We also thank Meritxell Deulofeu, Sílvia Prades and Adrià Ricarte for their contributions to the study as part of their final degree projects.

Funding

This study was supported by grants BFU2015-66109-R (Ministerio de Economia y Competitividad, MINECO/FEDER, EU) and 2017 SGR 621 (Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya). E.A.G. was supported by the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (FI-DGR 2015 Program) and by the Ministerio de Educación, Cultura y Deporte de España (FPU 2015).

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Authors and Affiliations

  1. Departament de Ciències Fisiològiques, Institut de Neurociènces, Universitat de Barcelona, Feixa Llarga s/n, 08907, L’Hospitalet de Llobregat, Catalunya, Spain

    Vanessa Martins-Lopes, Anna Bellmunt, Erin A. Greguske, Alberto F. Maroto & Jordi Llorens

  2. Institut d’Investigació Biomèdica de Bellvitge, IDIBELL, 08907, L’Hospitalet de Llobregat, Catalunya, Spain

    Erin A. Greguske, Alberto F. Maroto & Jordi Llorens

  3. Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, 17003, Girona, Catalunya, Spain

    Pere Boadas-Vaello

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  1. Vanessa Martins-Lopes
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  2. Anna Bellmunt
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  5. Pere Boadas-Vaello
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  6. Jordi Llorens
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Correspondence to Jordi Llorens.

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The use of the animals was in accordance with EU Directive 2010/63 as implemented by Law 5/1995 and Act 214/1997 of the Generalitat de Catalunya, and Law 6/2013 and Act 53/2013 of the Gobierno de España. The experiments were approved by the Ethics Committee on Animal Experimentation of the Universitat de Barcelona.

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Martins-Lopes, V., Bellmunt, A., Greguske, E.A. et al. Quantitative Assessment of Anti-Gravity Reflexes to Evaluate Vestibular Dysfunction in Rats. JARO 20, 553–563 (2019). https://doi.org/10.1007/s10162-019-00730-6

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