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GABAB receptors contribute to vestibular compensation after unilateral labyrinthectomy in pigmented rats
Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences.
2000 (English)In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 134, no 1, 32-41 p.Article in journal (Refereed) Published
Abstract [en]

The horizontal vestibulo-ocular reflex was studied in pigmented rats, which had been unilaterally, chemically labyrinthectomised 6–144 days previously. During this partially compensated stage after unilateral labyrinthectomy (UL), both static and dynamic deficits remain. The former was evaluated by recording of spontaneous eye movements in darkness, and the latter by estimating the slow-phase velocity (SPV) gain of compensatory eye movements during horizontal vestibular stimulation. The GABAB agonist baclofen caused a reversal of the remaining ipsilesional drift of the eyes in darkness into a nystagmus with a contralesional slow phase. The GABAB antagonist CGP 36742 caused a decompensation by exaggerating the remaining ipsilesional eye drift. Further, baclofen equilibrated or reversed the asymmetry between ipsi- and contralesional SPV gains during horizontal sinusoidal rotations at 0.2 Hz and 0.8 Hz. This was achieved by an increase in the ipsilesional gain and a decrease in the contralesional gain. The phase lead during sinusoidal rotation (0.2 Hz) was larger following rotation to the lesioned side than to the intact side in UL rats. This asymmetry was reversed by baclofen. CGP 36742 inhibited the effects of baclofen, while the antagonist per se aggravated SPV gain and phase lead asymmetries in UL rats during vestibular stimulation. Per- and post-rotatory nystagmus induced by velocity step stimulation revealed an imperfect velocity-storage function in UL animals, which was modulated by baclofen. An investigation of the baclofen effect on SPV gain asymmetry during different time intervals after chemical UL showed a completely developed effect on the 6th day. Bilateral flocculectomy did not alter the effects of baclofen on UL animals. It is concluded that physiological stimulation of GABAB receptors contributes to minimise the vestibulo-oculomotor asymmetry during the partially compensated period after UL. Administration of an agonist or an antagonist changes the asymmetry towards the ipsi- or contralesional side, possibly by altering the spontaneous neuronal activity in the bilateral medial vestibular nuclei. The results are compatible with a hypothesis, supported by in vitro slice experiments, that the efficacy of GABAB receptors is up-regulated on the ipsilesional side and down-regulated on the contralesional side.

Place, publisher, year, edition, pages
2000. Vol. 134, no 1, 32-41 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-25256DOI: 10.1007/s002210000438Local ID: 9695OAI: oai:DiVA.org:liu-25256DiVA: diva2:245584
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically 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.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 765
National Category
Medical and Health Sciences
Identifiers
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)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-19Bibliographically approved

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Magnusson, AnnaLindström, SivertTham, Richard

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