title: Saturation of long-term potentiation in the dorsal cochlear nucleus and its pharmacological reversal in an experimental model of tinnitus.
abstract: Animal models have demonstrated that tinnitus is a pathology of dysfunctional excitability in the central auditory system, in particular in the dorsal cochlear nucleus (DCN) of the brainstem. We used a murine model and studied whether acoustic over-exposure leading to hearing loss and tinnitus, affects long-term potentiation (LTP) at DCN multisensory synapses. Whole cell and field potential recordings were used to study the effects on release probability and synaptic plasticity, respectively in brainstem slices. Shifts in hearing threshold were quantified by auditory brainstem recordings, and gap-induced prepulse inhibition of the acoustic startle reflex was used as an index for tinnitus. An increased release probability that saturated LTP and thereby induced metaplasticity at DCN multisensory synapses, was observed 4-5days following acoustic over-exposure. Perfusion of an NMDA receptor antagonist or decreasing extracellular calcium concentration, decreased the release probability and restored LTP following acoustic over-exposure. In vivo administration of magnesium-threonate following acoustic over-exposure restored LTP at DCN multisensory synapses, and reduced gap detection deficits observed four months following acoustic over-exposure. These observations suggest that consequences of noise-induced metaplasticity could underlie the gap detection deficits that follow acoustic over-exposure, and that early therapeutic intervention could target metaplasticity and alleviate tinnitus.
authors.affiliation: Department of Neurosciences, Psychology and Behaviour, University of Leicester, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tagoe
authors.affiliation: Department of Neurosciences, Psychology and Behaviour, University of Leicester, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Deeping
authors.affiliation: Department of Neurosciences, Psychology and Behaviour, University of Leicester, UK. Electronic address: mh86@le.ac.uk.
authors.forename: Martine
authors.initials: M
authors.lastname: Hamann
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D017626:Cochlear Nucleus / Q000502:physiology*; D005260:Female; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008962:Models, Theoretical; D009474:Neurons / Q000502:physiology*; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate
keywords: Auditory; Central auditory system; Long-term potentiation; Release probability; Synapse; Synaptic plasticity