Residual inhibition: From the putative mechanisms to potential tinnitus treatment

Galazyuk, Alexander V.; Longenecker, Ryan J.; Voytenko, S.V.; Kristaponyte, Inga; Nelson, G.L.

doi:10.1016/j.heares.2019.01.022

Cited by 40 publications

(41 citation statements)

References 121 publications

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“…From results of ours and others, it is evident that enhanced inhibition from either presynaptic or postsynaptic side is sufficient to compensate for the reduced GABAergic system to interfere with tinnitus 64,65 . Given the addiction potential and other side-effects of benzodiazepam type drug, enhancing inhibitory effects using M-8324 is likely more therapeutically appealing.…”

Section: Enhanced Inhibition On Evoked and Spontaneous Activities M-mentioning

confidence: 52%

Increasing endogenous activity of NMDARs on GABAergic neurons increases inhibition, alters sensory processing and prevents noise-induced tinnitus

Deng

Masri

Yao

et al. 2020

Sci Rep

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Selective enhancement of GABAergic inhibition is thought to impact many vital brain functions and interferes with the genesis and/or progression of numerous brain disorders. Here, we show that selectively increasing nMDA receptor activity in inhibitory neurons using an nMDAR positive allosteric modulator (pAM) elevates spiking activity of inhibitory neurons in vitro and in vivo. in vivo infusion of pAM increases spontaneous and sound-evoked spiking in inhibitory and decreases spiking in excitatory neurons, and increases signal-to-noise ratio in the primary auditory cortex. in addition, pAM infusion prior to noise trauma prevents the occurrence of tinnitus and reduction in GABAergic inhibition. these results reveal that selectively enhancing endogenous nMDAR activity on the GABAergic neurons can effectively enhance inhibitory activity and alter excitatory-inhibitory balance, and may be useful for preventing diseases that involve reduced inhibition as the major cause.

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Section: Enhanced Inhibition On Evoked and Spontaneous Activities M-mentioning

confidence: 52%

Increasing endogenous activity of NMDARs on GABAergic neurons increases inhibition, alters sensory processing and prevents noise-induced tinnitus

Deng

Masri

Yao

et al. 2020

Sci Rep

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“…Equally, factors like duration or intensity of the stimuli are essential for its mode of action [Terry et al, 1983; Norena et al, 2002; Vernon and Fenwick, 1984; Neff et al, 2017]. In contrast, the underlying neurophysiological mechanisms of RI are not clearly understood yet [Roberts, 2007; Galazyuk et al, 2019]. Most recent work suggests that tinnitus suppression through sound stimulation is related to reduced spontaneous firing of central auditory neurons [Galazyuk et al, 2017, 2019].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the underlying neurophysiological mechanisms of RI are not clearly understood yet [Roberts, 2007; Galazyuk et al, 2019]. Most recent work suggests that tinnitus suppression through sound stimulation is related to reduced spontaneous firing of central auditory neurons [Galazyuk et al, 2017, 2019].…”

Section: Introductionmentioning

confidence: 99%

aMpLiTuDe MoDuLaTeD noise for tinnitus suppression in tonal and noise-like tinnitus

Schoisswohl

Arnds

Schecklmann

et al. 2019

Preprint

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Background: Acoustic stimulation offers a potential treatment approach for tinnitus but also insights in its basic mechanisms by short-term tinnitus suppression called residual inhibition (RI). The effects of RI were found to be depending on intensity, length or sound types covering the individual tinnitus characteristics. In patients with tonal tinnitus RI was increased with amplitude modulated (AM) pure tones at the individual tinnitus frequency while the effects of modulated noise sounds have not been systematically researched.Objectives: The aim of the present study was to investigate whether in patients with noise-like tinnitus RI can be increased by AM noise-like stimuli according to the individual tinnitus frequency range.Methods: For this purpose the individual tinnitus characteristics (noise-like and tonal tinnitus) were assessed via customizable noise-band matching, in order to generate bandpass filtered stimuli according to the individual tinnitus sound (individualized bandpass filtered sounds; IBP). Subsequent, various stimuli differing in bandpass filtering and AM were tested with respect to their potential to induce RI. Patients were acoustically stimulated with seven different types of stimuli for three minutes each and had to rate the loudness of their tinnitus after each stimuli.Results: Results indicate a general efficacy of noise stimuli for the temporary suppression of tinnitus, but no significant differences between AM and unmodulated IBP. Significantly better effects were observed for the subgroup with noise-like tinnitus (n=14), especially directly after stimulation offset. Conclusions:The study at hand provides further insights in potential mechanisms behind RI for different types of tinnitus. Beyond that, derived principles may qualify for new or extend current tinnitus sound therapies.Chronic subjective tinnitus is defined as the permanent perception of a sound such as ringing or 1 hissing in the absence of an external or internal source of noise. Approximately 10-15% of the 2 population in industrial countries experience this phantom sound [Langguth et al., 2013; Erlands-3 son and Dauman, 2013; Heller, 2003; Hall et al., 2011]. Causes for the development of tinnitus are 4 divergent and not completely understood, though most commonly tinnitus occurs towards cochlear 5 damages due to noise trauma [Langguth et al., 2013]. In the majority of cases, the perceived tin-6 nitus pitch is in accordance with the frequency spectrum of hearing loss (HL) [Basile et al., 2013; 7 Roberts et al., 2008]. As a consequence of decreased or absent auditory input and the subsequent 8 deficiency of neural input, maladaptive pathological changes in the auditory pathway are formed, 9 which lead to the perception of a "phantom sound" defined as tinnitus [Eggermont, 2007; Egger-10 mont and Tass, 2015; Eggermont and Roberts, 2012]. Neurophysiological investigations were able 11 to demonstrate hyperactivity in auditory brain areas [Farhadi et al., 2010; Folmer, 2007] as well as 12 aberrant oscillatory brain...

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“…The brainstem is the preliminary location of integrating complex auditory processes such as sound localization. Understanding the functions of mGluRs in auditory circuits will provide a deeper appreciation for modulatory mechanisms involved with auditory processing and help cultivate potential therapeutic approaches targeting mGluRs in treating hearing disorders such as tinnitus (ringing of the ear without external sound stimuli; reviewed by Galazyuk et al, 2019 ). Here, we review the studies on mGluRs in the avian ITD and the mammalian ILD circuits with a focus on brainstem structures.…”

Section: Introductionmentioning

confidence: 99%

Neuromodulation by mGluRs in Sound Localization Circuits in the Auditory Brainstem

Goel

Peng

2020

Front. Neural Circuits

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The ability of humans and animals to localize the source of a sound in a complex acoustic environment facilitates communication and survival. Two cues are used for sound localization at horizontal planes, interaural time and level differences (ITD and ILD), which are analyzed by distinct neural circuits in the brainstem. Here, we review the studies on metabotropic glutamate receptor (mGluR)-mediated neuromodulation of both intrinsic and synaptic properties of brainstem neurons in these circuits. Both mammalian and avian animal models have been used, with each having their advantages that are not present in the other. For the mammalian model, we discuss mGluR neuromodulation in the ILD circuit, with an emphasis on the recent discovery of differential modulation of synaptic transmission of different transmitter release modes. For the avian model, we focus on reviewing mGluR neuromodulation in the ITD pathway, with an emphasis on tonotopic distribution and synaptic plasticity of mGluR modulation in coincidence detector neurons. Future works are proposed to further investigate the functions and mechanisms of mGluRs in the sound localization circuits.

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Residual inhibition: From the putative mechanisms to potential tinnitus treatment

Cited by 40 publications

References 121 publications

Increasing endogenous activity of NMDARs on GABAergic neurons increases inhibition, alters sensory processing and prevents noise-induced tinnitus

Increasing endogenous activity of NMDARs on GABAergic neurons increases inhibition, alters sensory processing and prevents noise-induced tinnitus

aMpLiTuDe MoDuLaTeD noise for tinnitus suppression in tonal and noise-like tinnitus

Neuromodulation by mGluRs in Sound Localization Circuits in the Auditory Brainstem

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