Postnatal glutamatergic and GABAergic transmission within the vestibular nucleus is critical for the maturation of canal-related spatial map

Abstract

N-methyl-D-aspartate (NMDA) receptor and γ-aminobutyric acid (GABA) receptor play important roles in regulating the maturation of different sensory systems, including the visual, auditory and somatosensory systems. With the use of Fos protein expression as a neuronal marker for postsynaptic activation after sinusoidal horizontal rotation, we have revealed the occurrence of a spatial map in the inferior olive (IO) and thalamus, the descending and ascending relay stations of the vestibular circuitry respectively. To ascertain the contribution of excitatory and inhibitory inputs on the formation of spatial map in the central vestibular system, Elvax slice loaded with NMDA receptor antagonist MK801 or GABAA receptor antagonist bicuculline methoiodine was implanted over the bilateral vestibular nucleus (VN) of neonatal rats. The rats were allowed to recover until adulthood. We found that adult rats pretreated at P1 with MK801 or bicuculline could stay on rotating rod for shorter times than the controls. Comparable motor deficits were observed in animals either with selective destruction of IO cells by 3-acetylpyridine treatment or with electrolytic lesion of thalamic subnuclei that expressed horizontal rotation triggered Fos-positive neurons. Derangement of spatial map in IO and thalamus was also observed in both MK801-treated and bicuculline-treated adult rats, suggesting that postnatal NMDA and GABA transmission within VN is critical for developmental establishment of neural network for spatial map that encodes rotational motion in mature animals.