Skip to main content

Advertisement

SpringerLink
Log in

Glycine Receptor Deficiency and Its Effect on the Horizontal Vestibulo-ocular Reflex: a Study on the SPD1J Mouse

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

Abstract

Inhibition is critical in the pathways controlling the vestibulo-ocular reflex (VOR) and plays a central role in the precision, accuracy and speed of this important vestibular-mediated compensatory eye movement. While γ-aminobutyric acid is the common fast inhibitory neurotransmitter in most of the VOR microcircuits, glycine is also found in key elements. For example, the omnidirectional pause neurons (OPNs) and inhibitory burst neurons in the horizontal VOR both use glycine as their preferred inhibitory neurotransmitter. Determining the precise contribution of glycine to the VOR pathway has been difficult due to the lack of selective tools; however, we used spasmodic mice that have a naturally occurring defect in the glycine receptor (GlyR) that reduces glycinergic transmission. Using this animal model, we compared the horizontal VOR in affected animals with unaffected controls. Our data showed that initial latency and initial peak velocity as well as slow-phase eye movements were unaffected by reduced glycinergic transmission. Importantly however, there were significant effects on quick-phase activity, substantially reducing their number (30–70 %), amplitude (~55 %) and peak velocity (~38 %). We suggest that the OPNs were primarily responsible for the reduced quick-phase properties, since they are part of an unmodifiable, or more ‘hard-wired’, microcircuit. In contrast, the effects of reduced glycinergic transmission on slow-phases were likely ameliorated by the intrinsically modifiable nature of this pathway. Our results also suggested there is a ‘threshold’ in GlyR-affected animals, below which the effects of reduced glycinergic transmission were undetected.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

FIG. 1
FIG. 2
FIG. 3

Similar content being viewed by others

References

  • Bagnall MW, Zingg B, Sakatos A, Moghadam SH, Zeilhofer HU, du Lac S (2009) Glycinergic projection neurons of the cerebellum. J Neurosci 29:10104–10110

    Article  PubMed  CAS  Google Scholar 

  • Calabrese DR, Hullar TE (2006) Planar relationships of the semicircular canals in two strains of mice. J Assoc Res Otolaryngol 7:151–159

    Article  PubMed  Google Scholar 

  • Camp AJ, Lim R, Anderson WB, Schofield PR, Callister RJ, Brichta AM (2010) Attenuated glycine receptor function reduces excitability of mouse medial vestibular nucleus neurons. Neuroscience 170:348–360

    Article  PubMed  CAS  Google Scholar 

  • Cartwright AD, Gilchrist DP, Burgess AM, Curthoys IS (2003) A realistic neural-network simulation of both slow and quick phase components of the guinea pig VOR. Exp Brain Res 149:299–311

    PubMed  Google Scholar 

  • Curthoys IS (2002) Generation of the quick phase of horizontal vestibular nystagmus. Exp Brain Res 143:397–405

    Article  PubMed  CAS  Google Scholar 

  • Faucheux S, Schwaller B, Buizza A (2007) Automatic detection and removal of fast phases from nystagmographic recordings by optimal thresholding. Biomed Signal Process Control 2:144–150

    Article  Google Scholar 

  • Garbutt S, Harwood MR, Harris CM (2001) Comparison of the main sequence of reflexive saccades and the quick phases of optokinetic nystagmus. Br J Ophthalmol 85:1477–1483

    Article  PubMed  CAS  Google Scholar 

  • Graham BA, Schofield PR, Sah P, Margrie TW, Callister RJ (2006) Distinct physiological mechanisms underlie altered glycinergic synaptic transmission in the murine mutants spastic, spasmodic, and oscillator. J Neurosci 26:4880–4890

    Article  PubMed  CAS  Google Scholar 

  • Horn AK, Buttner-Ennever JA, Wahle P, Reichenberger I (1994) Neurotransmitter profile of saccadic omnipause neurons in nucleus raphe interpositus. J Neurosci 14:2032–2046

    PubMed  CAS  Google Scholar 

  • Leigh RJ, Zee DS (2006) The neurology of eye movements, 4th edn. Oxford University Press, New York

    Google Scholar 

  • Lisberger SG, Pavelko TA (1988) Brain stem neurons in modified pathways for motor learning in the primate vestibulo-ocular reflex. Science 242:771–773

    Article  PubMed  CAS  Google Scholar 

  • Malinvaud D, Vassias I, Reichenberger I, Rossert C, Straka H (2010) Functional organization of vestibular commissural connections in frog. J Neurosci 30:3310–3325

    Article  PubMed  CAS  Google Scholar 

  • Migliaccio AA, Minor LB, Carey JP (2004) Vergence-mediated modulation of the human horizontal vestibulo-ocular reflex is eliminated by a partial peripheral gentamicin lesion. Exp Brain Res 159:92–98

    Article  PubMed  Google Scholar 

  • Migliaccio AA, Macdougall HG, Minor LB, Della Santina CC (2005) Inexpensive system for real-time 3-dimensional video-oculography using a fluorescent marker array. J Neurosci Meth 143:141–150

    Article  Google Scholar 

  • Migliaccio AA, Della Santina CC, Carey JP, Minor LB, Zee DS (2006) The effect of binocular eye position and head rotation plane on the human torsional vestibuloocular reflex. Vis Res 46:2475–2486

    Article  PubMed  Google Scholar 

  • Migliaccio AA, Minor LB, Della Santina CC (2010) Adaptation of the vestibulo-ocular reflex for forward-eyed foveate vision. J Physiol 588:3855–3867

    Article  PubMed  CAS  Google Scholar 

  • Migliaccio AA, Meierhofer R, Della Santina CC (2011) Characterization of the 3D angular vestibulo-ocular reflex in C57BL6 mice. Exp Brain Res 210:489–501

    Article  PubMed  Google Scholar 

  • Moss SJ, Smart TG (2001) Constructing inhibitory synapses. Nat Rev Neurosci 2:240–250

    Article  PubMed  CAS  Google Scholar 

  • Optican LM (2008) The role of omnipause neurons: why glycine? Prog Brain Res 171:115–121

    Article  PubMed  Google Scholar 

  • Otero-Millan J, Macknik SL, Serra A, Leigh RJ, Martinez-Conde S (2011) Triggering mechanisms in microsaccade and saccade generation: a novel proposal. Ann NY Acad Sci 1233:107–116

    Article  PubMed  Google Scholar 

  • Ramachandran R, Lisberger SG (2008) Neural substrate of modified and unmodified pathways for learning in monkey vestibuloocular reflex. J Neurophysiol 100:1868–1878

    Article  PubMed  Google Scholar 

  • Ramat S, Somers JT, Das VE, Leigh RJ (1999) Conjugate ocular oscillations during shifts of the direction and depth of visual fixation. Invest Ophthalmol Vis Sci 40:1681–1686

    PubMed  CAS  Google Scholar 

  • Robinson DA (1976) Adaptive gain control of vestibuloocular reflex by the cerebellum. J Neurophysiol 39:954–969

    PubMed  CAS  Google Scholar 

  • Rossert C, Moore LE, Straka H, Glasauer S (2011) Cellular and network contributions to vestibular signal processing: impact of ion conductances, synaptic inhibition, and noise. J Neurosci 31:8359–8372

    Article  PubMed  Google Scholar 

  • Rucker JC, Ying SH, Moore W, Optican LM, Buttner-Ennever J, Keller EL, Shapiro BE, Leigh RJ (2011) Do brainstem omnipause neurons terminate saccades? Ann NY Acad Sci 1233:48–57

    Article  PubMed  Google Scholar 

  • Ryan SG, Buckwalter MS, Lynch JW, Handford CA, Segura L, Shiang R, Wasmuth JJ, Camper SA, Schofield P, O’Connell P (1994) A missense mutation in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor in the spasmodic mouse. Nat Genet 7:131–135

    Article  PubMed  CAS  Google Scholar 

  • Sakatani T, Isa T (2007) Quantitative analysis of spontaneous saccade-like rapid eye movements in C57BL/6 mice. Neurosci Res 58:324–331

    Article  PubMed  Google Scholar 

  • Saul B, Schmieden V, Kling C, Mulhardt C, Gass P, Kuhse J, Becker CM (1994) Point mutation of glycine receptor alpha 1 subunit in the spasmodic mouse affects agonist responses. FEBS Lett 350:71–76

    Article  PubMed  CAS  Google Scholar 

  • Schmucker C, Schaeffel F (2004) A paraxial schematic eye model for the growing C57BL/6 mouse. Vis Res 44:1857–1867

    Article  PubMed  Google Scholar 

  • Scudder CA, Fuchs AF (1992) Physiological and behavioral identification of vestibular nucleus neurons mediating the horizontal vestibuloocular reflex in trained rhesus monkeys. J Neurophysiol 68:244–264

    PubMed  CAS  Google Scholar 

  • Shin M, Moghadam SH, Sekirnjak C, Bagnall MW, Kolkman KE, Jacobs R, Faulstich M, du Lac S (2011) Multiple types of cerebellar target neurons and their circuitry in the vestibulo-ocular reflex. J Neurosci 31:10776–10786

    Article  PubMed  CAS  Google Scholar 

  • Spencer RF, Wenthold RJ, Baker R (1989) Evidence for glycine as an inhibitory neurotransmitter of vestibular, reticular, and prepositus hypoglossi neurons that project to the cat abducens nucleus. J Neurosci 9:2718–2736

    PubMed  CAS  Google Scholar 

  • Stahl JS, James RA, Oommen BS, Hoebeek FE, De Zeeuw CI (2006) Eye movements of the murine P/Q calcium channel mutant tottering, and the impact of aging. J Neurophysiol 95:1588–1607

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

A.A. Migliaccio was supported by a National Health and Medical Research Council of Australia (NHMRC) Biomedical CDA 568736 grant. P.P. Hübner was supported by a UNSW International Research scholarship and a NeuRA supplementary scholarship. R. Lim and A.M. Brichta were supported by NHMRC (APP101159) and the Garnett Passe and Rodney Williams Memorial Foundation. We would like to thank I.S. Curthoys for proofreading the manuscript and D.S. Zee for his suggestions.

Author information

Authors and Affiliations

  1. Balance and Vision Laboratory, Neuroscience Research Australia, Cnr Barker Street & Easy Street, Randwick, Australia, 2031

    Patrick P. Hübner & Americo A. Migliaccio

  2. University of New South Wales, Sydney, Australia

    Patrick P. Hübner & Americo A. Migliaccio

  3. The University of Newcastle, Callaghan, Australia

    Rebecca Lim & Alan M. Brichta

  4. Johns Hopkins University, Baltimore, USA

    Americo A. Migliaccio

Authors
  1. Patrick P. Hübner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rebecca Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alan M. Brichta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Americo A. Migliaccio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Americo A. Migliaccio.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hübner, P.P., Lim, R., Brichta, A.M. et al. Glycine Receptor Deficiency and Its Effect on the Horizontal Vestibulo-ocular Reflex: a Study on the SPD1J Mouse. JARO 14, 249–259 (2013). https://doi.org/10.1007/s10162-012-0368-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10162-012-0368-6

Keywords

Search

Navigation