Central vestibular compensation : the role of the GABAB receptor

Sammanfattning: 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.