GABAergic transmission in developmental establishment of a gravity-related spatial reference

Abstract

In rats, the subnuclei of the inferior olive (IO) and thalamus exist topographic spatial representation to sinusoidal horizontal linear translations along either the antero-posterior or interaural direction. To examine the effect of GABAergic neurotransmission within the vestibular nucleus on the establishment of gravity-related topographic spatial representation in relay station of the central vestibular pathway, GABAA receptor antagonist bicuculline was used to chronically perturb GABA transmission within the vestibular nucleus of postnatal rats. Implantation of bicuculline-loaded or saline-loaded Elvax slice onto the dorsal surface of vestibular nucleus was performed in P1 rats which were allowed to recover into adulthood. Fos protein expression was used as an indicator to identify central neurons responsive to horizontal linear accelerations. In stationary or labyrinthectomized rats, Fos-immunoreactive (ir) neurons were either absent or sporadically scattered throughout the IO and thalamic subnuclei, indicating that the Fos expression in these neural area was otolithic in origin. In the saline control group, Fos expression induced by horizontal antero-posterior linear acceleration was observed in both the IO and thalamus. Responsive IO subnuclei include β subnucleus of IO and dorsomedial cell column while those in the thalamus include central medial nucleus, paracentral nucleus, mediodorsal nucleus, central lateral nucleus, zona incerta and subparafascicular nucleus of thalamus. For-ir neurons responsive to horizontal interaural linear acceleration were found in those IO subnuclei and thalamic subnuclei. When compared with the saline-treated group, the number of Fos-ir IO neurons responsive to horizontal linear acceleration was significantly lower in adult rats perturbed with bicuculline at P1. Besides, the pattern of Fos expression in both the IO and thalamus was altered in adult rats pretreated with bicuculline. In the utricle-related thalamic subnuclei, the postnatal time when Fos-ir neurons were found triggered by otolithic stimulation was delayed and the number of these Fos-ir neurons was fewer in the bicuculline-treated group than those in the saline-treated group. To investigate whether there exists a critical period for postnatal establishment of topographic spatial representation in the IO and thalamus, implantation of bicuculline-loaded Elvax slice onto the vestibular nucleus was carried out in P14 rats. The topographic spatial representation in IO and thalamus of those rats were unchanged as compared with adult rats pretreated with saline at P14. These results indicate that the GABAergic neuronal circuit in the vestibular nucleus plays an important role in postnatal establishment of topographic spatial representation in the central vestibular system. Most importantly, we documented the occurrence of a postnatal critical period (between P1 and P14) during which GABAergic transmission regulated the formation of a gravity-related spatial framework in the brain.