Change in adult distribution pattern of otolith-related neurons in the inferior olive after perinatal blockade of gaba transmission in the vestibular nucleus

Abstract

γ-aminobutyric acid (GABA) is a major inhibitor neurotransmitter in vestibular nucleus (VN). Using c-fos expression as a marker for postsynaptic activation after sinusoidal linear acceleration along different horizontal axes, we examined the developmental distribution of otolith-related neurons along the vestibulo-olivary pathway of Sprague Dawley rats. While these neurons were found in all vestibular subnuclei, they were only observed in two subnuclei in downstream realy inferior olive (IO), viz. dorsomedial cell column and beta subnulclei. A progressive change in the distribution pattern was observed in these IO subnuclei during postnatal development. To further determine whether perinatal blockade of GABA transmission in the VN perturbs consequential formation of the internal spatial reference in the IO, we chronically blocked the GABA receptors in VN by implanting bicuculline-impregnated Elvax slice over the bilateral VN of rats at postnatal day 1 (P1). These animals were allowed to recover until P14, P21 and adulthood. In these bicuculline-treated rats, GABA receptor blockade led to a change in the distribution pattern as well as a decrease in Fos-expressing IO neurons in P14 and older rats. In saline-treated rats, the pattern of gravity-related horizontal orientations within the IO was maintained. Our findings therefore suggest that GABA neurotransmission within the VN is crucial for postnatal establishment of gravity-related internal spatial reference within the IO.