Tinnitus and inferior colliculus activity in chinchillas related to three distinct patterns of cochlear trauma

Abstract

A long-standing hypothesis is that tinnitus, the perception of sound without an external acoustic source, is triggered by a distinctive pattern of cochlear hair cell (HC) damage and this subsequently leads to altered neural activity in the central auditory pathway. This hypothesis was tested by assessing behavioral evidence of tinnitus and spontaneous neural activity in the inferior colliculus (IC) after unilateral cochlear trauma. Chinchillas were assigned to 4 cochlear treatment groups. Each treatment produced a distinctive pattern of HC damage. Acoustic exposure (AEx): sparse low-frequency inner hair cell (IHC) and outer hair cell (OHC) loss; round window cisplatin (CisEx): pronounced OHC loss mixed with some IHC loss; round window carboplatin (CarbEx): pronounced IHC loss without OHC loss; control: no loss. Compared to controls, all experimental groups displayed significant and similar psychophysical evidence of tinnitus with features resembling a 1 kHz tone. Contralateral IC spontaneous activity was elevated in the AEx and CisEx groups, which showed increased spiking and increased cross-fiber synchrony. A multi-dimensional analysis identified a subpopulation of neurons more prevalent in animals with tinnitus. These units were characterized by high bursting, low ISI variance, and within-burst peak spiking of approximately 1000/sec. It was concluded that cochlear trauma in general, rather than its specific features, leads to multiple changes in central activity that underpin tinnitus. Particularly affected was a subpopulation ensemble of IC neurons with the described unique triad of features.

Efferent Pathways Modulate Hyperactivity in Inferior Colliculus

“…These data are compared with the average spontaneous rates in the same CF regions seen 2 weeks after acoustic trauma (data from ). The increased incidence of neurons with a high spontaneous firing rate after acoustic trauma encountered in our experiments is in agreement with other studies (Wang et al, 1996(Wang et al, , 2002Imig and Durham, 2005;Ma et al, 2006;Brozoski et al, 2007;Bauer et al, 2008;Dong et al, 2009;). In the present study, only neurons with a spontaneous firing rate Ͼ8 spikes/s were selected for testing the effect of efferent stimulation.…”

“…This plasticity has been demonstrated in a wide range of animal models, using either mechanically, acoustically, or drug-induced cochlear lesions (Kaltenbach et al, 2000;Seki and Eggermont, 2003;Kaltenbach et al, 2004;Ma et al, 2006;Brozoski et al, 2007;Bauer et al, 2008;Dong et al, 2009Dong et al, , 2010). Hyperactivity has been suggested to be involved in the generation of tinnitus, an auditory phantom perception (Brozoski et al, 2002;Kaltenbach et al, 2004;Bauer et al, 2008).…”

“…This plasticity has been demonstrated in a wide range of animal models, using either mechanically, acoustically, or drug-induced cochlear lesions (Kaltenbach et al, 2000;Seki and Eggermont, 2003;Kaltenbach et al, 2004;Ma et al, 2006;Brozoski et al, 2007;Bauer et al, 2008;Dong et al, 2009Dong et al, , 2010). Hyperactivity has been suggested to be involved in the generation of tinnitus, an auditory phantom perception (Brozoski et al, 2002;Kaltenbach et al, 2004;Bauer et al, 2008). This hypothesis is supported by the fact that the hyperactivity seems restricted to tonotopic regions broadly corresponding to the area of hearing loss as shown in cochlear nucleus (CN), the central nucleus of the inferior colliculus (CNIC), and the auditory cortex (Kaltenbach et al, 2000;Komiya and Eggermont, 2000;Seki and Eggermont, 2003;Ma et al, 2006;Dong et al, 2009;) and the observation in human studies that there is a strong correlation between the tinnitus pitch and the hearing loss frequencies (Mühlnickel et al, 1998;Norena et al, 2002;Eggermont and Roberts, 2004).…”

Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition

“…The ability of FA imaging to reveal hyperactive auditory brainstem circuits in vitro is an important advancement in the field of tinnitus. Although hyperactivity may or may not be the cause of tinnitus (29,30), hyperactivity provides a reliable marker of tinnitus that has also been seen in the inferior colliculus and the auditory cortex (13,23,(31)(32)(33). Given that FA imaging allows for measurement of circuit activity levels at different auditory nuclei within the same animal, FA imaging experiments in vitro are expected to provide information about the development of tinnitus.…”

The mechanisms of tinnitus: Perspectives from human functional neuroimaging

“…Obviously, increased spontaneous firing rate within this region does increase the opportunity for synchronous activity, but there is reliable evidence that the increased synchrony is unlikely to be just a statistical artifact of spontaneous firing rate (Bauer et al, 2008). A computational model of TI describes the mechanism by which deafferentation can lead to increases in neural synchrony within the damaged region of the tonotopic map through compensatory decreases in the gain of lateral connections (Dominguez et al, 2006).…”