title: Acoustic over-exposure triggers burst firing in dorsal cochlear nucleus fusiform cells.
abstract: Acoustic over-exposure (AOE) triggers deafness in animals and humans and provokes auditory nerve degeneration. Weeks after exposure there is an increase in the cellular excitability within the dorsal cochlear nucleus (DCN) and this is considered as a possible neural correlate of tinnitus. The origin of this DCN hyperactivity phenomenon is still unknown but it is associated with neurons lying within the fusiform cell layer. Here we investigated changes of excitability within identified fusiform cells following AOE. Wistar rats were exposed to a loud (110 dB SPL) single tone (14.8 kHz) for 4 h. Auditory brainstem response recordings performed 3-4 days after AOE showed that the hearing thresholds were significantly elevated by about 20-30 dB SPL for frequencies above 15 kHz. Control fusiform cells fired with a regular firing pattern as assessed by the coefficient of variation of the inter-spike interval distribution of 0.19 ± 0.11 (n = 5). Three to four days after AOE, 40% of fusiform cells exhibited irregular bursting discharge patterns (coefficient of variation of the inter-spike interval distribution of 1.8 ± 0.6, n = 5; p < 0.05). Additionally the maximal firing following step current injections was reduced in these cells (from 83 ± 11 Hz, n = 5 in unexposed condition to 43 ± 6 Hz, n = 5 after AOE) and this was accompanied by an increased firing gain (from 0.09 ± 0.01 Hz/pA, n = 5 in unexposed condition to 0.56 ± 0.25 Hz/pA, n = 5 after AOE). Current and voltage clamp recordings suggest that the presence of bursts in fusiform cells is related to a down regulation of high voltage activated potassium currents. In conclusion we showed that AOE triggers deafness at early stages and this is correlated with profound changes in the firing pattern and frequency of the DCN major output fusiform cells. The changes here described could represent the initial network imbalance prior to the emergence of tinnitus.
authors.affiliation: Department of Cell Physiology and Pharmacology, Maurice Shock Medical Science Building, University of Leicester, University Road, Leicester LE1 9HN, UK.
authors.forename: Nadia
authors.initials: N
authors.lastname: Pilati
authors.forename: Charles
authors.initials: C
authors.lastname: Large
authors.forename: Ian D
authors.initials: ID
authors.lastname: Forsythe
authors.forename: Martine
authors.initials: M
authors.lastname: Hamann
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold; D017626:Cochlear Nucleus / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem; D006317:Hearing Loss, Noise-Induced / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008564:Membrane Potentials; D009622:Noise / Q000009:adverse effects*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014012:Tinnitus / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D024642:Potassium Channels, Voltage-Gated; D011188:Potassium
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