| Summary: | Inhibitory synaptic transmission within the vestibular circuits plays an essential
regulatory role in coordinating vestibular functions. The maturation profile of γ-
aminobutyric acid (GABA) synapses in the vestibular system remains unknown. To
address this, we first used double immunohistochemistry to document the postnatal
expression profile of GABAA receptors in canal-related and saccule-related vestibular
nuclear neurons of rats. The proportion of Fos / GABAA receptors α1 subunit doublelabeled
neurons progressively increased with age. Whole-cell patch-clamp experiments
on brainstem slice preparations were also employed to characterize the developmental
properties of these synapses within the medial vestibular nucleus. The frequency of
GABAA receptor-mediated miniature inhibitory postsynaptic currents (IPSC)
progressively increased during the first two postnatal weeks and reached a plateau
thereafter. This is in agreement with an increase in sensitivity to GABAA receptor α1
subunit agonist zolpidem during the same period. The rise time and decay time however
decreased by 2-fold. These results suggest that change in the composition of GABAA
receptor occurs during the functional maturation of medial vestibular neurons.
To further investigate whether GABA receptors contribute to synaptic plasticity in
the developing vestibular nucleus, two stimulus protocols were used. Repetitive
depolarizing pulses induced long-lasting decrease in the frequency of GABAA receptormediated
spontaneous IPSCs between P3 and P7. The probability of inducing such
frequency decline of sIPSCs decreased after the first postnatal week. High frequency
stimulation on the other hand, induced long-term depression (LTD) of GABAA receptormediated
evoked IPSCs between P3 and P5. The probability of inducing LTD decreased
after P14. These results indicate that LTD at GABAergic synapses could be easily
induced in developing medial vestibular neurons before maturation of GABAergic
synaptic transmission.
To examine if GABAergic transmission within the vestibular nucleus is crucial
for establishment of gravity-related spatial organization, an intervention approach was
adopted to perturb GABAergic transmission within the postnatal vestibular nucleus. A
slice of Elvax loaded with either GABAA receptor agonist muscimol or antagonist
bicuculline was inserted into the fourth ventricle and covered the bilateral vestibular
nuclei at different ages. Expression of Fos protein in functionally activated neurons was
used to demarcate the topographic spatial map in the inferior olive. The spatial map in
subnuclei IOβ and DMCC was disturbed in each adult rat that was implanted with
bicuculline- or muscimol-loaded Elvax at P1. However, no change was observed in
adult rats that were pretreated with bicuculline or muscimol at P14 or P21. Vestibularrelated
behavior tests were also performed. The acquisition of negative geotaxis, an
otolith-related orientation reflex, was delayed in postnatal rats pretreated with bicuculline
but was advanced in those rats pretreated with muscimol. Furthermore, the acquisition of
motor learning, evaluated by rotarod test, was impaired in adult rats treated with
bicuculline or muscimol.
Taken together, our results indicated that maturation of GABAergic transmission
within the vestibular nucleus play important roles in development of spatial recognition
and vestibular-related behavior. === published_or_final_version === Physiology === Doctoral === Doctor of Philosophy
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