Spontaneous hyperactivity in the auditory midbrain: Relationship to afferent input

Robertson, Donald; Bester, Christofer; Vogler, Darryl P.; Mulders, Wilhelmina

doi:10.1016/j.heares.2012.02.002

Cited by 75 publications

(68 citation statements)

References 21 publications

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“…Our previous work showed that the peripheral dependence of central hyperactivity is temporary [18], and that the central-intrinsic phase emerges at around 8 to 12 weeks post–trauma [27]. At this latter stage, both hyperactivity and tinnitus should become resistant to furosemide treatment and further animal studies are needed to test this hypothesis.…”

Section: Discussionmentioning

confidence: 98%

“…This drive comprises the spontaneous firing of surviving primary afferent neurons, which is still present despite the fact that acoustic trauma reduces sensitivity to sound. In the second stage, central neurons become so excitable that they begin to generate their own intrinsic spontaneous firing and hyperactivity therefore becomes relatively independent of peripheral afferent input [27]. If hyperactivity is involved in the development of tinnitus, this suggests there may be a therapeutic window for recent-onset tinnitus in the first stage, using treatments that reduce cochlear afferent firing.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Furosemide on Cochlear Neural Activity, Central Hyperactivity and Behavioural Tinnitus after Cochlear Trauma in Guinea Pig

2014

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Cochlear trauma causes increased spontaneous activity (hyperactivity) to develop in central auditory structures, and this has been suggested as a neural substrate for tinnitus. Using a guinea pig model we have previously demonstrated that for some time after cochlear trauma, central hyperactivity is dependent on peripheral afferent drive and only later becomes generated intrinsically within central structures. Furosemide, a loop diuretic, reduces spontaneous firing of auditory afferents. We investigated in our guinea pig model the efficacy of furosemide in reducing 1) spontaneous firing of auditory afferents, using the spectrum of neural noise (SNN) from round window recording, 2) hyperactivity in inferior colliculus, using extracellular single neuron recordings and 3) tinnitus at early time-points after cochlear trauma. Tinnitus was assessed using gap prepulse inhibition of acoustic startle (GPIAS). Intraperitoneal furosemide, but not saline, caused a marked decrease in both SNN and central hyperactivity. Intracochlear perfusion with furosemide similarly reversed central hyperactivity. In animals in which GPIAS measurements suggested the presence of tinnitus (reduced GPIAS), this could be reversed with an intraperitoneal injection with furosemide but not saline. The results are consistent with furosemide reducing central hyperactivity and behavioural signs of tinnitus by acting peripherally to decrease spontaneous firing of auditory afferents. The data support the notion that hyperactivity may be involved in the generation of tinnitus and further suggest that there may be a therapeutic window after cochlear trauma using drug treatments that target peripheral spontaneous activity.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Effects of Furosemide on Cochlear Neural Activity, Central Hyperactivity and Behavioural Tinnitus after Cochlear Trauma in Guinea Pig

2014

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“…Several studies at the next auditory center of the brain stem, the inferior colliculus (IC), have demonstrated increased SFRs just below, within and just above the noise-damaged region of the cochlea, which correlated with presence of tinnitus using GPIAS [48, 49], but in some studies [50, 51] the increased spontaneous activity was not dependent on the presence of tinnitus. Nonetheless, increases in IC spontaneous activity appear to be dependent on that transmitted from the DCN since DCN ablation prior to noise damage prevents IC hyperactivity as well as tinnitus development [52].…”

Section: Neurophysiological Alterations In Animal Models Of Tinnitusmentioning

confidence: 99%

Maladaptive plasticity in tinnitus — triggers, mechanisms and treatment

2016

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Tinnitus is a phantom auditory sensation that reduces quality of life for millions worldwide and for which there is no medical cure. Most cases are associated with hearing loss caused by the aging process or noise exposure. Because exposure to loud recreational sound is common among youthful populations, young persons are at increasing risk. Head or neck injuries can also trigger the development of tinnitus, as altered somatosensory input can affect auditory pathways and lead to tinnitus or modulate its intensity. Emotional and attentional state may play a role in tinnitus development and maintenance via top-down mechanisms. Thus, military in combat are particularly at risk due to combined hearing loss, somatosensory system disturbances and emotional stress. Neuroscience research has identified neural changes related to tinnitus that commence at the cochlear nucleus and extend to the auditory cortex and brain regions beyond. Maladaptive neural plasticity appears to underlie these neural changes, as it results in increased spontaneous firing rates and synchrony among neurons in central auditory structures that may generate the phantom percept. This review highlights the links between animal and human studies, including several therapeutic approaches that have been developed, which aim to target the neuroplastic changes underlying tinnitus.

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“…Type V and I units are assumed to receive direct or indirect inputs from the VCN, while type O units receive direct inputs from the DCN (Davis 2002;Ramachandran and May 2002). In the context of existing neurophysiological models, DCN-based hyperactivity is expected to target type O units (Kaltenbach 2006;Robertson et al 2013). Conversely, VCN-based hyperactivity is directed toward type V and I units (Vogler et al 2011).…”

Section: Surgical Preparation and Single-unit Recordingmentioning

confidence: 99%

Effects of Unilateral Acoustic Trauma on Tinnitus-Related Spontaneous Activity in the Inferior Colliculus

Ropp

Tiedemann

Young

et al. 2014

JARO

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This study describes the long-term effects of soundinduced cochlear trauma on spontaneous discharge rates in the central nucleus of the inferior colliculus (ICC). As in previous studies, single-unit recordings in Sprague-Dawley rats revealed pervasive increases in spontaneous discharge rates. Based on differences in their sources of input, it was hypothesized that physiologically defined neural populations of the auditory midbrain would reveal the brainstem sources that dictate ICC hyperactivity. Abnormal spontaneous activity was restricted to target neurons of the ventral cochlear nucleus. Nearly identical patterns of hyperactivity were observed in the contralateral and ipsilateral ICC. The elevation in spontaneous activity extended to frequencies well below and above the region of maximum threshold shift. This lack of frequency organization suggests that ICC hyperactivity may be influenced by regions of the brainstem that are not tonotopically organized. Sound-induced hyperactivity is often observed in animals with behavioral signs of tinnitus. Prior to electrophysiological recording, rats were screened for tinnitus by measuring gap pre-pulse inhibition of the acoustic startle reflex (GPIASR). Rats with positive phenotypes did not exhibit unique patterns of ICC hyperactivity. This ambiguity raises concerns regarding animal behavioral models of tinnitus. If our screening procedures were valid, ICC hyperactivity is observed in animals without behavioral indications of the disorder. Alternatively, if the perception of tinnitus is strictly linked to ongoing ICC hyperactivity, our current behavioral approach failed to provide a reliable assessment of tinnitus state.

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Spontaneous hyperactivity in the auditory midbrain: Relationship to afferent input

Cited by 75 publications

References 21 publications

Effects of Furosemide on Cochlear Neural Activity, Central Hyperactivity and Behavioural Tinnitus after Cochlear Trauma in Guinea Pig

Effects of Furosemide on Cochlear Neural Activity, Central Hyperactivity and Behavioural Tinnitus after Cochlear Trauma in Guinea Pig

Maladaptive plasticity in tinnitus — triggers, mechanisms and treatment

Effects of Unilateral Acoustic Trauma on Tinnitus-Related Spontaneous Activity in the Inferior Colliculus

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