Neural changes in the auditory cortex of awake guinea pigs after two tinnitus inducers: salicylate and acoustic trauma.

Tinnitus, also called phantom auditory perception, is a major health problem in western countries. As such, a significant amount of effort has been devoted to understanding its mechanisms, including studies in animals wherein a supposed "tinnitus state" can be induced. Here, we studied on the same awake animals the effects of a high-dose of salicylate and of an acoustic trauma both at levels known to induce tinnitus. Recordings of cortical activity (local field potentials) from chronically implanted electrodes in the same animals under each condition allowed direct comparison of the effects of salicylate and trauma (noise trauma was carried out several days after full recovery from salicylate administration). Salicylate induced a systematic and reversible increase in amplitude of cortical responses evoked by tone bursts over a wide range of frequencies and intensities. The effects of noise trauma, though much more variable than those of salicylate, resulted in both increases and decreases in the amplitude of cortical responses. These alterations of cortical response amplitudes likely reflect associated hypoacusis and hyperacusis. The effects of salicylate administration and noise trauma on spontaneous activity were also studied. Fourier analysis did not reveal any increase in power within any given frequency band; rather, both treatments induced a decrease of power spectrum over a relatively broad frequency band (approximately 10-30 Hz). Entropy rate of spontaneous activity, a measure of complexity (temporal correlations), was found to decrease after salicylate but not after acoustic trauma. The present data on evoked potentials confirm salicylate effects at the cortical level and partially extend such effects to acoustic trauma. While the present study showed that both salicylate and noise trauma induced some changes of spontaneous activity in auditory cortex, none of these changes are interpretable in terms of potential neural correlate of tinnitus.

Noreña AJ ，Moffat G ，Blanc JL ，Pezard L ，Cazals Y ... -  《-》

Salicylate induced neural changes in the primary auditory cortex of awake cats.

Systemic administration of salicylate at high doses can induce reversible tinnitus and hyperacusis in humans and animals. For this reason, a number of studies have investigated the salicylate-induced changes of neural activity in the auditory cortex (AC); however, most previous studies of the AC were conducted on brain slices or anesthetized animals, which cannot completely represent the actual conditions. Few efforts have been made to examine the neural activity of awake animals, and only recorded the local field potential (LFP) of the AC. In this study, we recorded neural spike activities from chronically implanted electrodes in the primary AC (A1) of awake cats, and investigated the changes of neural responses to pure-tone and click-train stimuli after systemic injection of 200 mg/kg salicylate. We found that sound-evoked spike activities were significantly increased from 1 h after salicylate administration, and the increase of neural responses lasted longer than 3 days with a peak at 12 h. Salicylate not only increased the amplitude of transient responses at the onset and offset of pure-tone stimuli, but also induced a sustained response during the prolonged stimulus period and a late response at ∼100 ms after stimulus offset. The significant enhancement of neural responses was observed over the entire tested frequency range (0.1-16 kHz) with a relative peak in the band of 3.2-9.6 kHz. The capability of exhibiting spikes synchronizing with successive clicks was also enhanced. All these effects were more apparent when the neurons were driven by high intensity sounds. Salicylate-administration also decreased the mean spontaneous rate in A1 units, and the decrease of spontaneous rate was larger in the units with a high initial spontaneous rate. Our data confirm that salicylate can modulate the neural activity at the cortical level and provide more information for understanding the mechanism of salicylate-induced tinnitus.

Zhang X ，Yang P ，Cao Y ，Qin L ，Sato Y ... -  《-》

Effects of the cannabinoid CB(1) agonist ACEA on salicylate ototoxicity, hyperacusis and tinnitus in guinea pigs.

Cannabinoids have been suggested as a therapeutic target for a variety of brain disorders. Despite the presence of their receptors throughout the auditory system, little is known about how cannabinoids affect auditory function. We sought to determine whether administration of arachidonyl-2'-chloroethylamide (ACEA), a highly-selective CB1 agonist, could attenuate a variety of auditory effects caused by prior administration of salicylate, and potentially treat tinnitus. We recorded cortical resting-state activity, auditory-evoked cortical activity and auditory brainstem responses (ABRs), from chronically-implanted awake guinea pigs, before and after salicylate + ACEA. Salicylate-induced reductions in click-evoked ABR amplitudes were smaller in the presence of ACEA, suggesting that the ototoxic effects of salicylate were less severe. ACEA also abolished salicylate-induced changes in cortical alpha band (6-10 Hz) oscillatory activity. However, salicylate-induced increases in cortical evoked activity (suggestive of the presence of hyperacusis) were still present with salicylate + ACEA. ACEA administered alone did not induce significant changes in either ABR amplitudes or oscillatory activity, but did increase cortical evoked potentials. Furthermore, in two separate groups of non-implanted animals, we found no evidence that ACEA could reverse behavioural identification of salicylate- or noise-induced tinnitus. Together, these data suggest that while ACEA may be potentially otoprotective, selective CB1 agonists are not effective in diminishing the presence of tinnitus or hyperacusis.

Berger JI ，Coomber B ，Hill S ，Alexander SPH ，Owen W ，Palmer AR ，Wallace MN ... -  《-》

Salicylate induced tinnitus: behavioral measures and neural activity in auditory cortex of awake rats.

Yang G ，Lobarinas E ，Zhang L ，Turner J ，Stolzberg D ，Salvi R ，Sun W ... -  《HEARING RESEARCH》

Tinnitus behavior and hearing function correlate with the reciprocal expression patterns of BDNF and Arg3.1/arc in auditory neurons following acoustic trauma.

Tan J ，Rüttiger L ，Panford-Walsh R ，Singer W ，Schulze H ，Kilian SB ，Hadjab S ，Zimmermann U ，Köpschall I ，Rohbock K ，Knipper M ... -  《NEUROSCIENCE》