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Early compensation of vestibulo-oculomotor symptoms after unilateral vestibular loss in rats is related to GABAB receptor function
Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
Institute for Hearing and Communication Research and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
2002 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 111, no 3, 625-634 p.Article in journal (Refereed) Published
Abstract [en]

The horizontal vestibulo-oculomotor reflex was studied in pigmented rats during the first 5 days after a unilateral chemical or surgical vestibular deafferentation. Spontaneous eye movements in darkness and slow phase velocity gain of compensatory eye movements during horizontal sinusoidal rotation were evaluated. The most evident vestibulo-oculomotor symptom immediately after a unilateral vestibular loss was a spontaneous nystagmus, which gradually abated during the following days. Further, an asymmetry between ipsi- and contra-lesional gains was evident during sinusoidal vestibular stimulation. Single systemic doses of the GABAB receptor antagonist [3-[1-(S)-[[3-(cyclohexylmethyl)-hydroxyphosphinoyl]-2-(S)-hydroxypropyl]amino]ethyl]-benzoic acid (CGP 56433A), the agonist baclofen, or the GABAA receptor agonist (4,5,6,7-tetrahydroisoxazolo-[5,4-c]-pyridin-3-ol (THIP) were given at different intervals after unilateral vestibular deafferentation. CGP 56433A highly aggravated the vestibulo-oculomotor symptoms, observed as an increase in spontaneous nystagmus and slow phase velocity gain asymmetry. This effect was most pronounced during the first 2 days after unilateral vestibular loss, when CGP 56433A even decompensated the vestibular system to the extent that all vestibular responses were abolished. Baclofen caused no effect during the first days after unilateral vestibular loss, but in parallel with the abatement of spontaneous nystagmus, the drug equilibrated or even reversed the remaining spontaneous nystagmus with corresponding effects on the slow-phase velocity gain asymmetry. The effects of baclofen were very similar after both chemical and surgical deafferentation. THIP caused a slight depression of all vestibular responses. All single dose effects of the drugs were transient.

Altogether these results reveal that endogenous stimulation of GABAB receptors in GABA-ergic vestibulo-oculomotor circuits are important for reducing the vestibular asymmetry during the early period after unilateral vestibular deafferentation. A possible role for GABAB receptors in the reciprocal inhibitory commissural pathways in the vestibular nuclei is suggested.

Place, publisher, year, edition, pages
2002. Vol. 111, no 3, 625-634 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-25264DOI: 10.1016/S0306-4522(01)00618-2Local ID: 9704OAI: diva2:245592
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-10-19Bibliographically approved
In thesis
1. Central vestibular compensation: the role of the GABAB receptor
Open this publication in new window or tab >>Central vestibular compensation: the role of the GABAB receptor
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The remarkable capacity for adaptive plastic changes in response to changed internal or external conditions is a distinctive feature of the vestibular system. Even in adults the system can be modified throughout life due to altered conditions caused by disease. trauma, medical treatment or normal ageing. Central nervous plastic changes following a unilateral peripheral vestibular loss are summarised by the term 'vestibular compensation'. This concept has become the most extensively investigated experimental model in studies of vestibular plasticity. The vestibular system governs a number of reflexes of which one is maintaining a stable gaze when the head moves - the vestibuloocular reflex. Since this reflex is relatively easy to quantify with non-invasive methods it constitutes an excellent tool for studying vestibular function in health and disease. Furthermore, the underlying neuronal circuitry of the reflex is phylogenetically ancient.

γ-Aminobutyric acid (GABA) is the most widely distributed inhibitory neurotransmitter in the vertebrate central nervous system. It acts via the classical GABAA and the more recently discovered GABAB receptors, the physiological functions of which are just beginning to emerge. The studies that provide the basis for this thesis systematically investigate the functional significance of the GABAB receptors for vestibular compensation during several stages after unilateral vestibular loss in rats. Firstly, the long-term maintenance of the partially normalised vestibular function weeks- months after the sensory loss was investigated (I and 11). Subsequently, the compensation that normalises the function of the vestibular system within a few days after the loss was investigated (III). Finally, in order to be able to investigate the acute stage, minutes - hours after unilateral vestibular loss, a method for reversible inactivation of the vestibular sensory input was developed (IV). In addition to information about the role of GABAB receptor function during this stage. the method also revealed the immediate behavioural consequences following a sudden transient vestibular loss as well as compensatory modulations that outlasted the inactivation of the sensory input (IV).

In summary, this thesis demonstrates a concrete physiological role of the GABAB receptors in a well-characterised neural system related to a specific behaviour. A direct causal relationship between the GABAB receptors and the physiological changes underlying compensation from a unilateral peripheral vestibular loss is established for all stages of the compensatory process. The physiological effect is partly mediated through an endogenous tonic control of the receptor. Furthermore, this thesis elucidates the immediate behavioural consequences of an acute transient loss of sensory vestibular input.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2003. 59 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 765
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-25687 (URN)10063 (Local ID)91-7373-522-1 (ISBN)10063 (Archive number)10063 (OAI)
Public defence
2003-01-16, Berzeliussalen, Hälsouniversitetet, Linköping, 09:00 (Swedish)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-19Bibliographically approved

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Magnusson, AnnaTham, Richard
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