Molecular mechanisms of brainstem plasticity. The vestibular compensation model.
Vestibular compensation is the process of behavioral recovery that occurs following unilateral deafferentation of the vestibular nerve fibers (unilateral labyrinthectomy, UL). Since UL results in a permanent loss of vestibular input from the ipsilateral vestibular (VIIIth) nerve, vestibular compensation is attributed to CNS plasticity and has been used as a general model of lesion-induced CNS plasticity. Behavioral recovery from the ocular motor and postural symptoms of UL is correlated with a partial return of resting activity to neurons in the vestibular nucleus (VN) on the deafferented side (the "deafferented VN"), and lesions to the deafferented VN prevent compensation; therefore, the regeneration of resting activity within the deafferented VN is believed to have a causal role in vestibular compensation. The biochemical mechanisms responsible for the adaptive neuronal changes within the deafferented VN are poorly understood. Neuropeptide hormone fragments, such as adrenocorticotrophic hormone (ACTH)-4-10, have been shown to accelerate vestibular compensation and can act directly on some VN neurons in vitro. Antagonists for the N-methyl-D-aspartate (NMDA) receptor have been shown to inhibit vestibular compensation if administered early in the compensation process. Biochemical studies in frog indicate marked alterations in the phosphorylation patterns of several proteins during compensation, and the in vitro phosphorylation of some of these proteins is modulated by ACTH-(1-24), calcium (Ca2+), and calmodulin or protein kinase C. It is therefore possible that ACTH fragments and NMDA antagonists (via their effects on NMDA receptor-mediated Ca2+ channels) modulate vestibular compensation through their action on Ca(2+)-dependent pathways within VN neurons. Recent studies have shown that some Ca2+ channel antagonists and the Ca(2+)-dependent enzyme inhibitor calmidazolium chloride facilitate vestibular compensation. How the regulation of Ca2+ may be related to the neuronal changes responsible for vestibular compensation is unclear at present.
Darlington
C L
CL
Department of Psychology, University of Otago, Dunedin, New Zealand.
Flohr
H
H
Smith
P F
PF
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000344:Afferent Pathways / Q000293:injuries; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003714:Denervation; D004292:Dominance, Cerebral; D007758:Ear, Inner / Q000293:injuries; D005133:Eye Movements / Q000502:physiology*; D008959:Models, Neurological; D009416:Nerve Regeneration; D009473:Neuronal Plasticity / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D011187:Posture / Q000502:physiology*; D011898:Ranidae / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D014725:Vestibular Nerve / Q000293:injuries; D014726:Vestibular Nuclei / Q000502:physiology*
D002121:Calcium Channel Blockers; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D000324:Adrenocorticotropic Hormone; C011394:ACTH (4-10); D002118:Calcium