Excitatory amino acid receptors in normal and abnormal vestibular function.

Abstract

Although excitatory amino acid (EAA) receptors have been investigated extensively in the limbic system and neocortex, less is known of the function of EAA receptors in the brainstem. A number of biochemical and electrophysiological studies suggest that the synapse between the ipsilateral vestibular (VIIIth) nerve and the brainstem vestibular nucleus (VN) is mediated by an EAA acting predominantly on kainate or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. In addition, there is electrophysiological evidence that input from the contralateral vestibular nerve via the contralateral VN is partially mediated by N-methyl-D-aspartate (NMDA) receptors. Input to the VN from the spinal cord may also be partially mediated by NMDA receptors. All of the electrophysiological studies conducted so far have used in vitro preparations, and it is possible that denervation of the VN during the preparation of an explant or slice causes changes in EAA receptor function. Nonetheless, these results suggest that EAA receptors may be important in many different parts of the vestibular reflex pathways. Studies of the peripheral vestibular system have also shown that EAAs are involved in transmission between the receptor hair cells and the vestibular nerve fibers. A number of recent studies in the area of vestibular plasticity have reported that antagonists for the NMDA receptor subtype disrupt the behavioral recovery that occurs following unilateral deafferentation of the vestibular nerve fibers (vestibular compensation). It has been suggested that vestibular compensation may be owing to an upregulation or increased affinity of NMDA receptors in the VN ipsilateral to the peripheral deafferentation; however; at present, there is no clear evidence to support this hypothesis.