AUDITORY AND VESTIBULAR SYSTEMS NEUROREPORT 0959-4965 & Lippincott Williams & Wilkins Vol 12 No 18 21 December 2001 3965 Tonic activity and GABA responsiveness of medial vestibular nucleus neurons in aged rats A. Him, A.R. Johnston, J.L.W. Yau 1 , J. Seckl 1 and M.B. Dutia CA Department of Biomedical Sciences, Hugh Robson Building, George Square, Edinburgh EH8 9XD; 1 Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK CA Corresponding Author Received 29 Auguast 2001; accepted 15 October 2001 The tonic discharge of rat medial vestibular nucleus (MVN) neurons, and their responsiveness to GABA receptor agonists were investigated in slices prepared from aged rats (24 months old). Aged MVN neurons showed regular spontaneous activity similar to that seen in slices from young adults. However the inhibitory effects of the GABA A agonist muscimol on the spontaneous activity of aged MVN neurons were signi®cantly greater than in young MVN neurons. Inhibitory responses to the GABA B agonist baclofen also tended to be greater in slices from aged animals, but this difference was not statistically signi®cant. The regular discharge of aged MVN neurons at ®ring rates similar to those in young animals suggests that the intrinsic excitability of MVN cells is main- tained with age. The up-regulation of GABA A receptor ef®cacy in aged MVN neurons may compensate for changes in inhibitory inputs from vestibular commissures and cerebellum that may occur with neuronal loss in the aged brain. Neuro- Report 12:3965±3968 & 2001 Lippincott Williams & Wilkins. Key words: Ageing; GABA receptors; Medial vestibular nucleus; Plasticity; Vestibular compensation INTRODUCTION Age-related changes in the vestibulo-ocular re¯exes (VORs) and de®cits in visual±vestibular interactions may contri- bute to disequilibrium, impaired visual acuity, dizziness and falls in the elderly. In aged people the horizontal VOR shows a systematic frequency- and amplitude-dependent deterioration suggestive of a progressive bilateral vestibu- lar loss, while visual±vestibular interactions are signi®- cantly impaired [1,2]. Degenerative changes in the peripheral and central parts of the vestibular system have been documented in aged animals and humans. In the periphery, a reduction in the number of vestibular hair cells and afferent nerve ®bers are seen in old humans [3± 5]. Sturrock [6] identi®ed an age-related loss of neurons in the lateral vestibular nucleus in the mouse. Alvarez et al. [7] and Lopez et al. [8] reported a decrease in the number of second-order neurons with increasing age in the vestib- ular nuclear complex in humans. In addition, the cerebel- lum, which plays an important role in the adaptive control of postural and oculomotor re¯exes, shows a decrease in Purkinje cell density with age [9]. In young adults the vestibulo-ocular system shows a high degree of synaptic and neuronal plasticity, which enables a substantial behavioral adaptation after drastic changes in peripheral afferent input. A particular example of such plasticity is vestibular compensation, the functional recovery that takes place after de-afferentation of one inner ear through unilateral labyrinthectomy (UL). This plasticity in the central vestibular pathways is presumably also involved throughout life in compensating for de®cits that arise from degenerative changes that occur with ageing. Recently we investigated the cellular mechanisms involved in vestibular compensation, and identi®ed two synergistic, adaptive responses of medial vestibular nucleus (MVN) neurons to de-afferentation. Within 4h of UL, MVN neurons up-regulate their intrinsic membrane excitability, and down-regulate the functional ef®cacy of their GABA A and GABA B receptors [10±13]. These changes are likely to be important in vestibular compensation, as they are appropriate to counteract the disfacilitation and increased commissural inhibition to which the MVN neurons are subjected immediately after UL (for discussion see [11,13]). In this study, we investigated the intrinsic spontaneous activity of MVN neurons in vitro, and their responsiveness to the GABA A and GABA B agonists muscimol and baclo- fen, in slices of the brain stem prepared from young adult and aged rats. In particular we were interested to deter- mine whether the reported delay in the rate of vestibular compensation after UL in aged animals [14] could be due to age-related changes in the intrinsic activity or GABA receptor sensitivity of the MVN neurons in old animals. MATERIALS AND METHODS Male Lister Hooded rats (Charles River, UK) were obtained at 2 months of age and maintained under conditions of controlled lighting (lights on 07.00±19.00 h) and tempera- Article number = nr121821