Glutamate Receptor Subunit and Calmodulin Kinase II Expression, with and without T Maze Training, in the Rat Hippocampus following Bilateral Vestibular Deafferentation

Abstract

Many previous studies have shown that lesions of the peripheral vestibular system result in spatial memory deficits and electrophysiological dysfunction in the hippocampus. Given the importance of glutamate as a neurotransmitter in the hippocampus, it was predicted that bilateral vestibular deafferentation (BVD) would alter the expression of NMDA and AMPA receptors in this area of the brain.MethodsThe expression of the NR1, NR2A, NR2B, GluR1, GluR2, GluR3 and GluR 4 glutamate receptor subunits, as well as calmodulin kinase IIα (CaMKIIα) and phosphorylated CaMKIIα (pCaMKIIα), was measured in the rat CA1, CA2/3 and dentate gyrus (DG) subregions of the hippocampus, at 24 h, 72 h, 1 week, 1 month and 6 months following BVD, using western blotting. In the 6 month group, half of the animals underwent spatial forced alternating training in a T-maze.Results and DiscussionFor the 24 h, 72 h, 1 week and 1 month data, there was no significant effect of surgery for any hippocampal subregion. However, for the 6 month data set, T maze training had a significant effect independently of surgery. The results of these experiments suggest that BVD is not associated with large changes in glutamate receptor subunit or CaMKIIα expression in the rat hippocampus, at least in terms of both the intra-cytoplasmic and membrane receptor subunits together, that western blotting can measure. However, spatial training-associated increases in glutamate receptor and CaMKIIα expression can be induced in BVD rats with impaired spatial performance. Therefore, the neurophysiological changes underlying BVD-induced spatial learning and memory deficits are more likely to be due to up and down regulation or changes in affinity/efficacy of glutamate receptors at the membrane level than changes in subunit transcription and transduction at the intra-cytoplasmic level.

Vestibular loss promotes procedural response during a spatial task in rats

“…Fragmentary data reported an increase in membrane NMDA receptor density within the hippocampus one month after bilateral chemical lesion , and a modulation of NMDA receptor subunits after surgical unilateral vestibular lesion in rats (Liu et al, 2003). However Zheng et al (2013), did not find same change in NMDA receptor subunits in hippocampus following bilateral vestibular lesion. In this study, we raised the question whether or not the endogenous levels of cAMP and the hippocampo-striatal ratio where influenced by the loss of vestibular lesion.…”

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“…It is often said that a patient ‘stops walking when talking' [67,68]. Also spatial learning and memory are affected by loss of labyrinthine input, probably influenced by the hippocampus, which is subject to functional and structural changes [52,69,70]. A bilateral atrophy of the hippocampus was found in 17% of a BVH population, which correlated with spatial memory deficits [71,72].…”

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