Molecular Analysis of Excitatory Amino Acid Receptor Expression in the Cochlea

Niedzielski, Andrew S.; Safieddine, Saaïd; Wenthold, Robert J.

doi:10.1159/000259232

Cited by 35 publications

(16 citation statements)

References 15 publications

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“…Cochlear NMDA receptors have been detected in a number of mammalian species. Their presence in the mammalian cochlea is supported by a body of evidence ranging from in situ hybridization histochemistry (Kuriyama et al, 1993;Niedzielski et al, 1997;Safieddine and Eybalin, 1992) to pharmacological (Chen et al, 2001;Ehrenberger and Felix, 1991;Felix and Ehrenberger, 1989;1990;Ostreicher et al, 2002;Pujol et al, 1992;1993), physiological (Kleinlogel et al, 1999;Puel et al, 1997) and electrophysiological investigations Puel et al, 1991). NMDA receptors have also been detected in the human cochlea (Nordang et al, 2000).…”

Section: Introductionmentioning

confidence: 94%

Bi-phasic intensity-dependent opioid-mediated neural amplitude changes in the chinchilla cochlea: Partial blockade by an N-Methyl-d-Aspartate (NMDA)-receptor antagonist

Sahley

Anderson

Chernicky

2008

European Journal of Pharmacology

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Dynorphins, glutamate, and glutamate-sensitive N-Methyl-D-Aspartate (NMDA) receptors exist in the mammalian cochlea. Dynorphins produce neural excitation and excitotoxic effects in the spinal cord through a κ-opioid facilitation of NMDA receptor sensitivity to glutamate. The κ-opioid receptor drug agonists N-dimethylallyl-normetazocine [(-)-pentazocine (50 mmol)] and trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide [U-50488H (100 mmol)] were administered across the cochlear round window membrane in the chinchilla. Each drug produced significant post-baseline amplitude changes in the click-evoked auditory nerve compound action potential. Amplitude changes at threshold amounted to increases in sensitivity that ranged from 4-8 decibels, measured in sound pressure level (dB SPL). The large neural amplitude increases at threshold were accompanied by progressively smaller amplitude changes at 5 and 10 dB above threshold (dB SL). However, at stimulus intensities ≥ 20dB SL, post-baseline neural amplitudes were suppressed to levels below baseline and control values. These bi-phasic intensity-dependent neural amplitude changes have never before been observed following i.v. administered (-)-pentazocine in this species. Finally, the bi-phasic neural amplitude changes in U-50488H-treated (100 mmol) animals were partially blocked (except at 20dB SL), following a round window pretreatment with the NMDA receptor drug antagonist, dizocilpine hydrogen maleate [(+)-MK-801 (8 mmol)]. Our data suggests that endogenous dynorphins within lateral efferent olivocochlear neurons differentially modulate auditory neural excitation, possibly through cochlear NMDA receptors and glutamate. The role played by lateral efferent opioid neuromodulation at cochlear NMDA receptors, is discussed.

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Section: Introductionmentioning

confidence: 94%

Bi-phasic intensity-dependent opioid-mediated neural amplitude changes in the chinchilla cochlea: Partial blockade by an N-Methyl-d-Aspartate (NMDA)-receptor antagonist

Sahley

Anderson

Chernicky

2008

European Journal of Pharmacology

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“…Glutamate is the major excitatory transmitter used at the synapses between hair cells and spiral ganglion neurons, and both ionotropic and metabotropic glutamate receptors are expressed in the cochlea (reviewed in Eybalin, 1993; Niedzielski et al, 1997). Of the group I mGluRs, messenger RNA (mRNA) for mGluR1 has been detected in both type I and type II neurons in cochlear ganglion cells of the rat and guinea pig (Safieddine and Eybalin, 1995).…”

Section: Anatomy and Physiology Of Mglurs In The Mammalian Cochleamentioning

confidence: 99%

Metabotropic glutamate receptors in auditory processing

2014

Neuroscience

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As the major excitatory neurotransmitter used in the vertebrate brain, glutamate activates ionotropic and metabotropic glutamate receptors (mGluRs), which mediate fast and slow neuronal actions, respectively. Important modulatory roles of mGluRs have been shown in many brain areas, and drugs targeting mGluRs have been developed for treatment of brain disorders. Here, I review the studies on mGluRs in the auditory system. Anatomical expression of mGluRs in the cochlear nucleus has been well characterized, while data for other auditory nuclei await more systematic investigations at both the light and electron microscopy levels. The physiology of mGluRs has been extensively studied using in vitro brain slice preparations, with a focus on the lower auditory brainstem in both mammals and birds. These in vitro physiological studies have revealed that mGluRs participate in neurotransmission, regulate ionic homeostasis, induce synaptic plasticity, and maintain the balance between excitation and inhibition in a variety of auditory structures. However, very few in vivo physiological studies on mGluRs in auditory processing have been undertaken at the systems level. Many questions regarding the essential roles of mGluRs in auditory processing still remain unanswered and more rigorous basic research is warranted.

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“…The in situ hybridization method described in this study is a modification of previously described protocols (Safieddine and Eybalin, 1992b;Safieddine et al, 1996;Niedzielski et al, 1997). Sections were treated with 0.2 M HC l for 20 min at room temperature and then washed in 1ϫ PBS for 10 min.…”

Section: Rt-pcrmentioning

confidence: 99%

The Glutamate Receptor Subunit δ1 Is Highly Expressed in Hair Cells of the Auditory and Vestibular Systems

Safieddine

Wenthold

1997

J. Neurosci.

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In the inner ear, fast excitatory synaptic transmission is mediated by ionotropic glutamate receptors, including AMPA, kainate, and NMDA receptors. The recently identified ␦1 and ␦2 glutamate receptors share low homology with the other three types, and no clear response or ligand binding has been obtained from cells transfected with ␦ alone or in combination with other ionotropic receptors. Studies of mice lacking expression of ␦2 show that this subunit plays a crucial role in plasticity of cerebellar glutamatergic synapses. In addition, these mice show a deficit in vestibular compensation. These findings and the nature of glutamatergic synapses between vestibulocochlear hair cells and primary afferent dendrites suggest that ␦ receptors may be functionally important in the inner ear and prompted us to investigate the expression of ␦ receptors in the cochlea and peripheral vestibular system. Reverse transcription and DNA amplification by PCR combined with immunocytochemistry and in situ hybridization were used. Our results show that the expression of ␦1 in the organ of Corti is intense and restricted to the inner hair cells, whereas ␦1 is expressed in all spiral ganglion neurons as well as in their satellite glial cells. In the vestibular end organ, ␦1 was highly expressed in both hair cell types and also was expressed in the vestibular ganglion neurons. The prominent expression of ␦1 in inner hair cells and in type I and type II vestibular hair cells suggests a functional role in hair cell neurotransmission. Key words: cochlea; vestibular end organ; hair cells; spiral ganglion neurons; PCR; in situ hybridization; Western blot; immunocytochemistryAuditory and vestibular stimuli are detected by hair cells in the inner ear and are transmitted to the brain by way of the auditory and vestibular nerves. Of the two types of hair cells found in the organ of Corti, inner hair cells (IHC s) and outer hair cells (OHC s), IHC s are the primary transducers of sensory information. IHC s form chemical synapses with dendrites of type I spiral ganglion neurons (SGNs) that constitute 90 -95% of the SGNs. OHC s synapse on the remaining type II SGNs (Spoendlin, 1972;Berglund and Ryugo, 1987). The vestibular epithelium contains two types of sensory hair cells. T ype I cells (V HCI) are flaskshaped and surrounded by an afferent nerve caly x, whereas type

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Molecular Analysis of Excitatory Amino Acid Receptor Expression in the Cochlea

Cited by 35 publications

References 15 publications

Bi-phasic intensity-dependent opioid-mediated neural amplitude changes in the chinchilla cochlea: Partial blockade by an N-Methyl-d-Aspartate (NMDA)-receptor antagonist

Bi-phasic intensity-dependent opioid-mediated neural amplitude changes in the chinchilla cochlea: Partial blockade by an N-Methyl-d-Aspartate (NMDA)-receptor antagonist

Metabotropic glutamate receptors in auditory processing

The Glutamate Receptor Subunit δ1 Is Highly Expressed in Hair Cells of the Auditory and Vestibular Systems

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