Neurochemical mechanisms of recovery from peripheral vestibular lesions (vestibular compensation)

This paper reviews the literature relating to the neurochemical basis of vestibular compensation, a process of behavioral recovery which occurs following the removal of afferent input from one labyrinth (unilateral labyrinthectomy, UL). Although vestibular compensation is known to be correlated with a return of resting activity to the vestibular nucleus (VN) ipsilateral to the UL (the deafferented VN), the neurochemical mechanisms by which this neuronal recovery occurs, are unknown. At present, there is little evidence to support the hypothesis that denervation supersensitivity of excitatory amino acid, dopamine, norepinephrine or acetylcholine receptors in the deafferented VN, is responsible for vestibular compensation: binding studies for glutamate or acetylcholine do not support an upregulation of these receptor types. However, changes in the affinity or efficacy of these receptor complexes cannot be ruled out. There are still many neurotransmitter systems, such as serotonergic and histaminergic systems, which have not been investigated in relation to vestibular compensation. In several species it has been shown that treatment with adrenocorticotropic hormone, fragment 4-10 (ACTH-(4-10], can accelerate vestibular compensation. It is not clear how these drugs exert their effects. In vitro electrophysiological studies have shown that VN neurons are capable of generating resting activity in the absence of their normal afferent inputs and it is possible that these neurons have pacemaker-like membrane characteristics which contribute to the regeneration of activity following UL. Recent biochemical studies have revealed changes in the phosphorylation patterns of a number of proteins during compensation. The possible relationship between these phosphorproteins and the synaptic or membrane changes which are responsible for vestibular compensation remains to be determined.