The selective AMPA receptor antagonist GYKI 53784 blocks action potential generation and excitotoxicity in the guinea pig cochlea

Ruel, Jérôme; Bobbin, Richard P.; Vidal, David; Pujol, Rémy; Puel, Jean–Luc

doi:10.1016/s0028-3908(00)00069-1

Cited by 80 publications

(76 citation statements)

References 34 publications

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“…The afferent synapse between OHCs and type II cochlear nerve fibers is poorly understood. It is not clear whether afferent transmission there is glutamatergic (33,34); glutamate excitotoxicity is not seen in the OHC area after acoustic overstimulation (33,34), and the efferent synapses on OHCs are clearly cholinergic in nature with end effects mediated via the ␣9/␣10 nicotinic acetylcholine receptors (9,40). Thus, it is difficult to propose a compelling argument as to why GluR␦1 loss should enhance damage to OHCs per se.…”

Section: Discussionmentioning

confidence: 99%

Orphan Glutamate Receptor δ1 Subunit Required for High-Frequency Hearing

Gao

Maison

et al. 2007

Molecular and Cellular Biology

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The function of the orphan glutamate receptor delta subunits (GluR␦1 and GluR␦2) remains unclear. GluR␦2 is expressed exclusively in the Purkinje cells of the cerebellum, and GluR␦1 is prominently expressed in inner ear hair cells and neurons of the hippocampus. We found that mice lacking the GluR␦1 protein displayed significant cochlear threshold shifts for frequencies of >16 kHz. These deficits correlated with a substantial loss of type IV spiral ligament fibrocytes and a significant reduction of endolymphatic potential in high-frequency cochlear regions. Vulnerability to acoustic injury was significantly enhanced; however, the efferent innervation of hair cells and the classic efferent inhibition of outer hair cells were unaffected. Hippocampal and vestibular morphology and function were normal. Our findings show that the orphan GluR␦1 plays an essential role in high-frequency hearing and ionic homeostasis in the basal cochlea, and the locus encoding GluR␦1 represents a candidate gene for congenital or acquired high-frequency hearing loss in humans.

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Section: Discussionmentioning

confidence: 99%

Orphan Glutamate Receptor δ1 Subunit Required for High-Frequency Hearing

Gao

Maison

et al. 2007

Molecular and Cellular Biology

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“…The swelling of afferent dendrites under IHCs can be mimicked by cochlear perfusion of glutamate receptor agonists such as kainate (Ruel et al 2000). Pharmacological studies suggest that this excitotoxicity is mediated by AMPA-type receptors (Ruel et al 2000), which are expressed by both cochlear and vestibular neurons (Niedsielski and Wenthold 1995). In the present study, vacuolization in the IHC area (Fig.…”

Section: Mechanisms Of Noise Damagementioning

confidence: 99%

Dynamics of Noise-Induced Cellular Injury and Repair in the Mouse Cochlea

Wang

Hirose

Liberman

2002

JARO

486

450

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To assess the dynamics of noise-induced tissue injury and repair, groups of CBA/CaJ mice were exposed to an octave-band noise for 2 hours at levels of 94, 100, 106, 112, or 116 dB SPL and evaluated at survival times of 0, 12, 24 hours or 1, 2, or 8 weeks. Functional change, assessed via auditory brainstem response (ABR), ranged from a reversible threshold shift (at 94 dB) to a profound permanent loss (at 116 dB). Light microscopic histopathology was assessed in serial thick plastic sections and involved quantitative evaluation of most major cell types within the cochlear duct, including hair cells (and their stereocilia), supporting cells, ganglion cells, spiral ligament ®-brocytes, spiral limbus ®brocytes, and the stria vascularis. Morphometry allowed patterns of damage to be systematically assessed as functions of (1) cochlear location, (2) exposure level, and (3) postexposure survival. Insights into mechanisms of acute and chronic noise-induced cellular damage are discussed.

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“…In the mammalian cochlea, the IHC/type I afferent synapse is clearly glutamatergic and excitatory: There is both pharmacological (Ruel et al 2000) and immunohistochemical (Matsubara et al 1996) evidence that fast transmission at this synapse is mediated by AMPA-type glutamate receptors. The afferent synapse between OHCs and type II neurons is less well understood.…”

Section: Cochlear Expression Of Gaba B Receptors and Sources Of Gabaementioning

confidence: 99%

Loss of GABAB Receptors in Cochlear Neurons: Threshold Elevation Suggests Modulation of Outer Hair Cell Function by Type II Afferent Fibers

Maison

Casanova

Bettler

et al. 2008

JARO

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Despite pharmacological and immunohistochemical evidence for GABA as a neurotransmitter in the olivocochlear efferent bundle, a clear functional role of GABA in the inner ear has not emerged. To explore the role of metabotropic GABA B receptors, we characterized the cochlear phenotype of mice with targeted deletion of the GABA B1 subunit and determined its tissue localization using a mouse line expressing a GFP-tagged GABA B1 subunit under the endogenous promoter. Immunostaining revealed GABA B1 expression in both type I and type II ganglion cells and in their synaptic terminals under inner and outer hair cells, respectively. No GABA B1 expression was observed in hair cells. Mean cochlear thresholds, measured via both auditory brainstem responses and distortion product otoacoustic emissions (DPOAEs), were elevated by ∼10 dB in GABA B1 -deficient mice, consistent with outer hair cell dysfunction. Olivocochlear efferent function, assessed via DPOAE suppression during efferent electrical stimulation, was unaffected by GABA B1 deletion. GABA B1 -deficient mice showed increased resistance to permanent acoustic injury, with mean threshold shifts ∼25 dB smaller than wild-types after exposure to 8-16-kHz noise at 100 dB for 2 h. In contrast, there was no vulnerability difference to temporary acoustic injury following exposure to the same noise at 94 dB for 15 min. Our results suggest that GABAergic signaling in type II afferent neurons may be required for normal outer hair cell amplifier function at low sound levels and may also modulate outer hair cell responses to highlevel sound.

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The selective AMPA receptor antagonist GYKI 53784 blocks action potential generation and excitotoxicity in the guinea pig cochlea

Cited by 80 publications

References 34 publications

Orphan Glutamate Receptor δ1 Subunit Required for High-Frequency Hearing

Orphan Glutamate Receptor δ1 Subunit Required for High-Frequency Hearing

Dynamics of Noise-Induced Cellular Injury and Repair in the Mouse Cochlea

Loss of GABAB Receptors in Cochlear Neurons: Threshold Elevation Suggests Modulation of Outer Hair Cell Function by Type II Afferent Fibers

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