Damage to the vestibular inner ear causes long-term changes in neuronal nitric oxide synthase expression in the rat hippocampus

The vestibular inner ear detects head acceleration and initiates compensato ry eye movement and postural reflexes that help keep the visual image of th e world stable on the retina, and maintain balance, during unexpected head movement. The most primitive vestibular systems are estimated to have evolv ed more than 500 million years ago and in mammalian and submammalian specie s the vestibular reflexes are mediated by basic brainstem pathways (see Wil son and Melvill Jones, 1979 for review). Although the contributions of the vestibular system to higher cognitive function have generally received less attention than its reflexive roles, vestibular sensory information is tran smitted to higher centres in the brain and humans with vestibular damage ar e known to experience debilitating perceptual illusions (see Curthoys and H almagyi, 1995; Berthoz, 1996 for reviews). Increasing behavioural and neuro physiological evidence suggests that the hippocampus uses information from the vestibular inner ear in order to build up maps of space that can be use d in the development of spatial memory during learning tasks (McNaughton et al., 1991; Chapuis et al., 1992; Wiener and Berthoz, 1993; O'Mara et al., 1994; Wiener et al., 1995; Gavrilov et al., 1995; Stackman and Taube, 1996; Vitte et al., 1996; Taube et al., 1996; Save et al., 1998; Peruch et al., 1999; Cuthbert et al., 2000; Russell et al., 2000). However, to date, there has been no indication of the long-term neurochemical effects of the loss of vestibular input on hippocampal function. Since nitric oxide has been im plicated in the mechanisms of hippocampal synaptic plasticity associated wi th the development of short-term memory (e.g. Schuman and Madison, 1991; Sc human et al., 1994; Arancio et al., 1996; Wu et al., 1997; Lu et al., 1999) , we examined whether changes occur in the activity and expression of the e nzymes responsible for nitric oxide production (nitric oxide synthases) in subregions of the rat hippocampus at different times following unilateral p eripheral vestibular lesions, using western blotting and radioenzymatic ass ays. We found a decreased expression of neuronal nitric oxide synthase in t he ipsilateral dentate gyrus at 2 weeks following the vestibular damage and not before, that may be related to the long-term effects of the loss of ve stibular input on hippocampal function. These results support the hypothesi s that head movement and position information derived from the vestibular i nner ear may be important for the normal function of the hippocampus. (C) 2 001 IBRO. Published by Elsevier Science Ltd. All rights reserved.