Abstract
There has been speculation into connections between the basal ganglia and the vestibular system for the last century. However, the results of studies investigating these connections have been inconsistent and controversial. Studies have not been systematic and use a variety of animal models, stimulations, and measurements. Electrophysiological studies of field potentials in animals have shown that most areas of the striatum respond to electrical vestibular stimulation, while human studies isolated responses to vestibular stimulation to the putamen of the striatum. Protein studies have shown inconsistent results regarding changes in receptor levels of a number of receptor types. While traditional thinking has postulated possible pathways between the vestibular system and the striatum, via the cortical connections, recent tracer studies have identified a pathway between the vestibular nucleus and the striatum via the thalamus, completely bypassing the cortex. This suggests the possibility that there are multiple pathways between the vestibular system and the striatum. The aim of this thesis was to identify if, how, and where, vestibular signals affect the function of striatal neurons.
For all of the studies presented within this thesis, electrical stimulation (100 Hz, square wave) was delivered to the round window of the inner ear of urethane-anaesthetised rats. Stimulation of the vestibular system was confirmed via the visualisation of vestibular nystagmus. For the electrophysiological study, we investigated the effects of brief electrical stimulation of the vestibular labyrinth. Single-unit responses were found bilaterally, with a response latency of approximately 50 ms from the end of the stimulus. A Bayesian credible interval for the percentage of neurons responding to vestibular stimulation, was estimated to be between 0.4 and 2.0%. For the c-Fos study, rats were allocated to a sham control group or one of two stimulation groups: the threshold for induction of vestibular nystagmus or twice that intensity. Stimulation was delivered for 10 min and the number of neurons expressing c-Fos in the striatum was quantified at 90 min following the stimulation using stereological methods.
Stimulation at 2x the threshold for nystagmus resulted in a significant decrease in the number of neurons expressing c-Fos in the bilateral striatum compared to both the sham control group and the lower stimulus intensity group. Microdialysis in the striatum was performed with HPLC-ECD analysis to identify neurochemical changes in response to stimulation at varying intensities. It was found that serine and dopamine levels in the striatum decrease compared to sham animals in response to electrical stimulation.
The results of this study demonstrate that: 1) some striatal neurons respond to electrical vestibular stimulation, however, these responses, at least under urethane anaesthesia, are circumscribed and infrequent; 2) electrical stimulation of the vestibular labyrinth results in a decrease in the number of striatal neurons expressing c-Fos, in a current-dependent manner; 3) Neurochemical changes, in response to electrical vestibular stimulation, are limited mostly to dopamine and serine. These results suggest there may be multiple pathways for vestibular signals to the striatum, and that these may have clinical implications in the treatment of basal ganglia disorders and other movement disorders.