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Saturation of long-term potentiation in the dorsal cochlear nucleus and its pharmacological reversal in an experimental model of tinnitus

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journal contribution
posted on 22.02.2017, 11:03 by Thomas Tagoe, Daniel Deeping, Martine Hamann
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 4–5 days 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.

Funding

This study was funded by Action on Hearing Loss (MR/J006556/1) (PhD studentship to TT) and Medical Research Council (AHL S12). Open Access funded by Medical Research Council

History

Citation

Experimental Neurology, 2017, 282, pp. 1-10

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Neuroscience, Psychology and Behaviour

Version

VoR (Version of Record)

Published in

Experimental Neurology

Publisher

Elsevier for Academic Press

issn

0014-4886

eissn

1090-2430

Acceptance date

14/02/2017

Copyright date

2017

Available date

22/02/2017

Publisher version

http://www.sciencedirect.com/science/article/pii/S0014488617300456

Language

en