Biomedical subjects

J L Puel

Publications and source records attributed to J L Puel.

At least 37 records · Page 2Linked to original sources

PubMed1995

Chemical synaptic transmission in the cochlea.

The last two decades have witnessed major progress in the understanding of cochlear mechanical functioning, and in the emergence of cochlear neurochemistry and neuropharmacology. Recent models describe active processes within the cochlea that amplify and sharpen the mechanical response to sound. Although it is widely accepted that outer hair cells (OHCs) contribute to these processes, the nature of the medial efferent influence on cochlear mechanics needs further clarification. Acetylcholine (ACh) is the major transmitter released onto OHCs during the stimulation of these efferents. The inhibitory influence of this system is mediated by post- and presynaptic nicontinic and muscarinic receptors and the role of other neuroactive substances [gamma-aminobutyric acid (GABA), calcitonin gene-related peptide (CGRP), adenosine 5'-triphosphate (ATP) or nitric oxide (NO)] remains to be determined. The inner hair cells (IHCs) that transduce the mechanical displacements into neural activity, release glutamate on receptor-activated channels of AMPA, kainate, and NMDA types. This synapse is in turn controlled and/or regulated by the lateral efferents containing a cocktail of neuroactive substances (ACh, GABA, dopamine, enkephalins, dynorphin, CGRP). This glutamatergic nature of the IHCs is responsible for the acute destruction of the nerve endings and subsequently for neuronal death, damage usually described in various cochlear diseases (noise-induced hearing losses, neural presbycusis and certain forms of sudden deafness or peripheral tinnitus). These pathologies also include a regrowth of new dendritic processes by surviving neurons up to IHCs. Understanding the subtle molecular mechanisms which underly the control of neuronal excitability, synaptic plasticity and neuronal death in cochlear function and disease is a very important issue for the development of future therapies.

Adenosine↗

PubMed1995

Effects of a dopaminergic agonist in the guinea pig cochlea.

This study investigates the role of dopamine, a putative lateral efferent neurotransmitter/modulator, in cochlear physiology and physiopathology. Cochlear potentials were recorded in guinea pigs after intracochlear perfusion of increasing doses (0.1-1 mM) of piribedil, an agonist of the D2/D3 receptors. A dose-dependent reduction in the amplitude of auditory nerve compound action potential (CAP) was observed, predominantly at high-intensity tone-burst stimulations, and without significant effect on CAP threshold. There was no variation of cochlear microphonic and summating potential. When 1 mM piribedil was perfused into the cochlea during continuous 130 dB SPL pure tone exposure (6 kHz, 15 min), CAP threshold shifts were significantly less than in control animals with artificial perilymph-perfused cochleas. No dendritic damage was observed, although there was evident hair cell damage. Similarly, radial dendrites were clearly protected against ischemia-induced damage when 1 mM piribedil was applied prior to a 10-min ischemia. These results suggest that dopamine modulates the activity of radial afferent fibers via D2/D3 receptors. The protective effect of piribedil during acoustic trauma or ischemia suggests that this modulation corresponds to a prevention of excitotoxicity due to dysfunction of inner hair cell neurotransmission.

Acoustic Stimulation↗

PubMed1995

Synaptic regeneration and functional recovery after excitotoxic injury in the guinea pig cochlea.

Cochlear ischemia and acoustic trauma result in an immediate hearing loss accompanied by the complete disruption of the terminal dendrites of primary auditory neurons postsynaptic to the sensory inner hair cells (IHCs). This synaptic uncoupling, due to an acute glutamate (IHC neurotransmitter) excitotoxicity process, can be mimicked by glutamate agonists. Thus, we have followed over a 5-day period the responses of guinea-pig cochleas to a local application of 200 microM AMPA. This application immediately results in a destruction of all postsynaptic endings of the auditory nerve, resulting in a total loss of cochlear potentials. Twenty-four hours after this excitotoxic injury, the inner hair cells were contacted by repaired postsynaptic dendrites and the cochlear potential had partially recovered. This process of neo-synaptogenesis was completed and the potentials were fully restored at 5 days post exposure. As shown by in situ hybridization, an up-regulation of NMDA and metabotropic glutamate receptors in the primary auditory neurons occurred during this process of recovery. This process of neo-synaptogenesis and functional recovery probably accounts for restoring hearing after temporary losses due to excitotoxic-related pathologies.

Animals↗

PubMed1994

Excitatory amino acid antagonists protect cochlear auditory neurons from excitotoxicity.

Since ischemic damage in the brain is linked to glutamate excitotoxicity, the effects of an acute exposure to glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) or N-methyl-D aspartate (NMDA) on the radial dendrites were compared with those occurring after a severe cochlear ischemia. Glutamate and AMPA, but not NMDA, produced a drastic swelling restricted to the radial dendrites below the inner hair cells (IHCs). At a concentration of 20 microM AMPA, a full electrophysiological recovery could be observed in some cochleas after washing the drug out. A prior perfusion of 6-7-dinitroquinoxaline-2,3-dione (DNQX, 50 microM) prevented the 25 microM AMPA-induced dendritic swelling. No protective effect of D-2-amino-5-phosphonopentanoate (D-AP5) could be observed. In the same way, ischemia (5-40 minutes) resulted in a clear swelling of the radial dendrites. While D-AP5 had no protective effects, 50 microM DNQX protected most of the radial dendrites from the ischemia-induced swelling, excepting those contacting the modiolar side of the IHCs. Finally, 50 microM DNQX + 50 microM D-AP5 resulted in a nearly complete protection of all the radial dendrites. Altogether, these results suggest that the acute swelling of radial dendrites primarily occurs via AMPA/kainate receptors. However, in radial dendrites contacting the inner hair cells on their modiolar side, NMDA receptors may be also involved.

2-Amino-5-phosphonovalerate↗

PubMed1993

Pathophysiology of the glutamatergic synapses in the cochlea.

The synapses between the inner hair cells (IHCs) and the radial auditory dendrites are thought to be glutamatergic. Besides its fast excitatory properties, glutamate is known to be neurotoxic when released in excess or incompletely recycled. In the cochlea, this may occur in two pathological conditions: ischemia and noise trauma. We have further investigated the acute excitotoxicity (i.e. the swelling of type I afferent dendrites) by electron microscopy processing on guinea pig cochleas after an ischemic exposure lasting 5 to 40 min. The radial auditory dendrites reacted to ischemia in a time-dependent manner, with the swelling extending when the duration of ischemia increased. The type and the specificity of swelling were comparable to what acutely occurs after an exposure to glutamate analogs such as kainic acid or AMPA. A protection against this swelling was obtained by perfusing the cochlea with glutamate antagonists prior to ischemia. DNQX, an antagonist at AMPA/kainate receptors, had a powerful protective effect, and almost complete protection was obtained by perfusing both DNQX and D-AP5 (a NMDA antagonist). The latter results indicate that the two classes of glutamate receptors (AMPA/kainate and NMDA), both found to be electrophysiologically active at the IHC-auditory nerve synapse, are also involved in the excitotoxic processes. In addition, we also report data involving dopamine (its D2 agonist piribedil) a putative neurotransmitter at the lateral efferent synapses, in a postsynaptic protection of primary auditory neurons during transient ischemia. Altogether, these findings constitute a promising pharmacological approach of cochlear pathologies such as neural presbycusis.

Animals↗

PubMed1993

Changes in 2f1-f2 distortion product otoacoustic emissions following alterations of cochlear metabolism.

This paper summarizes the results obtained from investigations in which distortion product otoacoustic emissions (DPOAEs) were studied together with other cochlear physiological parameters. The cochlear metabolism was subjected to three different experimental conditions: guinea pigs were either submitted to hypoxia, to an intra-cochlear perfusion of ouabain or to an intra-cochlear perfusion of naloxone. The data show that DPOAEs remain affected for a certain time after the metabolic perturbations were removed. The comparison of the behaviour of DPOAEs and of other cochlear parameters gives good indications on the way these different experimental procedures affect the functioning of the cochlea during and after their application.

Acoustic Stimulation↗

PubMed1992

Implication of non-NMDA and NMDA receptors in cochlear ischemia.

We have investigated the hypothesis that the acute ischemic swelling of the radial dendrites connected to the inner hair cells (IHCs) is mediated by glutamatergic receptors. In control cochleas, after 20 min ischemia all the dendrites were dramatically swollen. Conversely, after a perfusion of 50 microM 6-7-dinitroquinoxaline-2,3-dione (DNQX) before ischemia, most dendrites were protected although those contacting the IHCs on their modiolar side frequently swelled. After 50 microM of D-2-amino-5-phosphonopentanoate (D-AP5), no dendrite protection could be obtained. Finally, after DNQX and D-AP5, no dendrite swelling occurred. These results suggest that, in the cochlea, the acute ischemic swelling of dendrites primarily occurs via non-NMDA receptors. However, in radial dendrites contacting the IHCs on their modiolar side, NMDA receptors may contribute to excitotoxicity.

2-Amino-5-phosphonovalerate↗

PubMed1991

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid electrophysiological and neurotoxic effects in the guinea-pig cochlea.

We have recorded cochlear potentials after perilymphatic perfusion of cumulative doses of the excitatory amino acid alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) which selectively recognizes the non-N-methyl-D-aspartate ionotropic receptor formerly known as the quisqualate receptor. Our results show that AMPA (1-80 microM) caused a significant suppression of the amplitude of the compound action potential evoked by acoustic stimulation. A total elimination of this potential at the 100 microM concentration was observed in all animals. In no case was the cochlear microphonic potential, a hair cell receptor potential, affected by AMPA. Histological examinations were performed either at the end of the physiological studies or on cochleas perfused for 10 min with a single dose of AMPA (50 or 100 microM). In both experimental conditions, a selective dendritic swelling or radial afferent nerve endings under the sensory inner hair cells was observed. No damage was found in both types of hair cells supporting cells, lateral and medial efferent fibers and spiral afferent nerve ending on the outer hair cells. The occurrence of the radial dendrite swelling was prevented when 6,7-dinitroquinoxaline-2,3-dione (500 microM) was perfused in the cochlea 10 min prior, then concomitantly with AMPA. The present study strongly suggests that non-N-methyl-D-aspartate receptors, possibly of the AMPA subtype, are involved in the synaptic transmission between the inner hair cells and the primary auditory neurons. They provide further support for the hypothesis that L-glutamate, or another excitatory amino acid, acts as an inner hair cell neurotransmitter.

Acoustic Stimulation↗

PubMed1991

Electrophysiological evidence for the presence of NMDA receptors in the guinea pig cochlea.

An excitatory amino acid, possibly L-glutamate, which probably acts as a neurotransmitter at the inner hair cell-afferent fiber synapses in the cochlea. In the present study, we have used an electrophysiological approach to investigate at this level the presence of a major type of excitatory amino acid receptor, namely the glutamatergic receptor for which N-methyl-D-aspartate is a selective agonist. Our results show that, when N-methyl-D-aspartate and the antagonist 2-amino-5-phosphonovalerate are perfused through the perilymphatic scalae, they induced, by different mechanisms, a significant reduction of the amplitude of the compound action potential and an increase of the N1 latency, both predominant at high intensity tone burst stimulations. No significant difference was found in the presence or absence of Mg2+ in the artificial perilymph used as a vehicle. A further slight N-methyl-D-aspartate-induced decrease of the amplitude of the compound action potential, although non significant, was observed when the Mg2(+)-free perilymph contained 100 or 1000 microM glycine. In all the experimental conditions, no effect was observed on the cochlear microphonic potential. This observation is consistent with an action of N-methyl-D-aspartate and 2-amino-5-phosphonovalerate at receptors located on the auditory nerve dendrites contacting the inner hair cells. In conclusion, our results suggest the presence of N-methyl-D-aspartate receptors in the cochlea.

2-Amino-5-phosphonovalerate↗

PubMed1991

Cochlear origin of 2f1-f2 distortion products assessed by using 2 types of mutant mice.

Mutant mice with a particular type of cochlear pathology are excellent models to study the functional role of various structures in the cochlea. In order to assess the contribution of inner and outer hair cells to the generation of distortion product emissions (DPEs) we have recorded the 2f1-f2 DPE in a control group of CBA mice, which have normal numbers of inner and outer hair cells and two different types of mutant mice: the Bronx-waltzer mice and the Wv/Wv mice. In the Bronx waltzer mutant mice, 70% of inner hair cells are missing whereas the outer hair cells are present in normal number. The distortion product emissions 2f1-f2 is clearly recordable with a 10-20 dB lower magnitude as compared to normal CBA control mice. The homozygous Wv/Wv mutant mice on the other hand present a selective outer hair cell loss as a constant defect with no progressive degeneration of the organ of Corti and an essentially normal inner hair cell population. The cubic distortion products 2f1-f2 could not be detected in all but one animal. Therefore, the present study strongly suggests, that the outer hair cells are critically involved in the production of DPEs.

Animals↗

PubMed1990

Acetylcholine, carbachol, and GABA induce no detectable change in the length of isolated outer hair cells.

The mechanical and electrical properties of cochlear outer hair cells (OHCs) are suggested to modulate transduction by inner hair cells. These properties of OHCs are presumably regulated by efferent neurons which use several transmitters including acetylcholine (Ach) and gamma aminobutyric acid (GABA). Since it had been suggested that Ach causes isolated OHCs to shorten visibly, this study was designed to investigate whether GABA also alters the length of OHCs. OHCs were isolated from the guinea pig cochlea by mechanical dispersion after collagenase treatment. Cells were initially selected by strict morphological criteria. In addition they were only included in further studies if they attained a constant length during 10 min of superfusion with buffer solution. Neither GABA (20 microM: 100 microM), Ach (5 mM; 10 microM with 10 microM eserine) or carbachol (10 microM; 100 microM) altered OHC length when applied in iso-osmotic Hank's balanced salt solution (total number of cells tested, 72). If a change in length occurred it must have been smaller than 0.3 microns, our detection ability. In contrast, high potassium and variations in osmolarity changed hair cell length by 3-10% in agreement with other reports.

Acetylcholine↗

PubMed1990

Effect of contralateral sound stimulation on the distortion product 2F1-F2: evidence that the medial efferent system is involved.

The mechanical nonlinearity of the cochlea that is associated with normal cochlear function, induces distortion products that can be recorded in the external auditory canal. The acoustic cubic distortion product 2F1-F2 (DP) was measured in the external canal in the presence and in the absence of a contralateral white noise. The experiments were carried out on 20 guinea pigs after a section of the middle ear muscles. They showed that the presence of a contralateral white noise induces a significant reversible reduction of the magnitude of the DPs. This suppressive effect produced by the contralateral white noise was completely canceled out by the midline sagittal section of the brainstem. This report supports the hypothesis that the suppressive effect of a contralateral sound stimulation is mediated by the medial efferent system.

Acoustic Stimulation↗

PubMed1990

Salicylate, mefenamate, meclofenamate, and quinine on cochlear potentials.

The perilymphatic spaces of guinea pig cochleae were perfused with artificial perilymph, with and without drug, at a rate of 2.5 microliters/minute for 10 minutes. The compound action potential of the auditory nerve, cochlear microphonics, and the summating potential evoked by 10 kHz tone bursts of varying intensities were recorded from a wire inserted in the basal turn scala vestibuli. The endocochlear potential was recorded from the scala media. Sodium salicylate (1.25 to 10 mmol/L) reduced the magnitude of the compound action potential evoked by low-sound intensities without affecting the compound action potential evoked by high-sound intensities. Sodium salicylate also reduced cochlear microphonics and had no effect on summating potential. Cochlear perfusions of prostaglandin synthesis inhibitors, mefenamate (200 mumol/L), and meclofenamate (200 mumol/L), had no effect on the cochlear potentials. Quinine (10 to 100 mumol/L) reduced the compound action potential input-output function in a parallel fashion rather than selectively affecting the low-intensity compound action potential. Quinine (100 mumol/L) reduced cochlear microphonics and summating potential. Neither quinine (100 mumol/L) nor salicylate (5 mmol/L) affected endocochlear potential. These results suggest that salicylate-induced hearing loss is not caused by either antagonism of the hair cell transmitter or cyclooxygenase inhibition, nor is it caused by the same mechanism that causes quinine-induced hearing loss.

Acetates↗

PubMed1990

Glutamate neurotoxicity in the cochlea: a possible consequence of ischaemic or anoxic conditions occurring in ageing.

Glutamate is considered to be one of the most common neurotransmitters in the fast excitatory synapses in the central nervous system. On the other hand, its excitotoxic properties are increasingly cited to explain some of the brain damage linked with hypoxia and ischaemia: i.e., those that occur frequently in ageing. An excess release of glutamate could, either directly or indirectly, activate receptors on the postsynaptic neuron, causing ion influxes accompanied by a massive entry of water, which would lead to an acute swelling of dendrites. In addition, calcium influx deregulates calcium homeostasis, which could lead to cell death. In the cochlea, glutamate is now considered to be one of the best candidates to mediate neurotransmission between inner hair cells (IHCs) and the auditory nerve dendrites. Among the variety of anatomical and physiological findings supporting the glutamate hypothesis, is the striking similarity of acute damage in the organ of Corti caused by exposure to a glutamate analogue (kainic acid), or by hypoxia, or even by an intense loud noise. In all cases an immediate swelling is observed, specifically affecting the radial afferents below the IHCs. The best explanation for this swelling is related to glutamate (or glutamate analogue) excitotoxicity. Thus, some of the cochlear damage that occur with ageing, especially the loss of the radial afferent fibres and type I ganglion cells, might well be attributed to glutamate excitotoxicity linked to vascular atrophy. The present paper discusses this hypothesis.

Aging↗

PubMed1989

The quinoxalinediones DNOX, CNOX and two related congeners suppress hair cell-to-auditory nerve transmission.

We tested 6,7-dinitroquinoxaline-2,3-dione (DNQX); 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); 6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylic acid (DHQC); and 3-hydroxy-2-quinoxalinecarboxylic acid (3HQC), new kainate and quisqualate receptor antagonists, upon cochlear potentials in guinea pig. Perilymph spaces of guinea pig cochleae were perfused with artificial perilymph solutions containing up to 1000 microM concentrations of DHQC and 3HQC, and 500 microM concentrations of DNQX and CNQX, at a rate of 2.5 microliters/min for 10 min. Cochlear potentials evoked by 10 kHz tone bursts of varying intensity were recorded from the basal turn scala vestibuli. Cochlear perfusion of the four drugs resulted in a dose-related suppression of the compound action potential of the auditory nerve (CAP; N1-P1), a prolongation of N1 latency at suprathreshold levels, an elevated CAP threshold, and a decreased N1 latency at CAP threshold. None of the drugs had significant effects on cochlear microphonics (CM) or the summating potential (SP). EC50 values (concentrations causing a 50% reduction in CAP amplitude at 68 dB SPL) were 8 microM for DNQX, 30 microM for DHQC, 35 microM for CNQX, and 1 mM for 3HQC. Results support the hypothesis that kainate and quisqualate receptors are involved in neurotransmission between the hair cell and afferent nerve.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1989

Suppression of auditory nerve activity in the guinea pig cochlea by 1-(p-bromobenzoyl)-piperazine-2,3-dicarboxylic acid.

1-(p-Bromobenzoyl)-piperazine-2,3-dicarboxylic acid (pBB-PzDA; 0.03-5 mM), an excitatory amino acid antagonist, was perfused through the guinea pig cochlea while monitoring various cochlear potentials. pBB-PzDA (1-5 mM) reversibly suppressed the amplitude of the compound action potential of the auditory nerve (CAP) and increased the latency of N1 (the first negative wave of the CAP) at all sound intensities. pBB-PzDA had no detectable effect on N1 latency at CAP threshold or presynaptic potentials such as the cochlear microphonics and the summating potential. At the single-cell level pBB-PzDA (5 mM) reversibly suppressed the firing of single auditory nerve ganglion cells. pBB-PzDA appeared to have the same potency in the cochlea as kynurenic acid. We conclude that the mechanism of action of pBB-PzDA is consistent with an antagonism of the hair-cell transmitter at the afferent auditory nerve.

Acoustic Stimulation↗

PubMed1989

Comparative actions of salicylate on the amphibian lateral line and guinea pig cochlea.

1. Salicylate actions on afferent nerve activity in the Xenopus lateral line and on cochlear potentials in guinea pig were investigated. 2. In the lateral line, salicylate (0.3-2.5 mM) suppressed spontaneous activity, water motion evoked excitation and responses to L-glutamate (1-2 mM) and kainate (10-20 microM). 3. In the guinea pig, salicylate (0.6-10 mM) suppressed the compound action potential (CAP) and increased N1 latency at low but not high sound intensities. 4. In the lateral line salicylate action may involve an antagonism of the hair-cell transmitter on the afferent nerve. 5. In the cochlea salicylate may suppress the active process or cochlear amplifier.

Action Potentials↗

PubMed1988

Selective attention modifies the active micromechanical properties of the cochlea.

The micromechanical properties of the cochlea accounting for the exquisite properties of sensitivity and frequency selectivity depend on the integrity of an active biomechanism probably based upon a motile activity of outer hair cells (OHCs). Evoked oto-acoustic emissions (EOAEs), i.e. sounds emitted by the cochlea in response to a click, reflect this active biomechanism. We demonstrate here that a selective attention task in human subjects alters EOAEs. This means that the central nervous system can modify active cochlear micromechanics prior to the transduction process, probably by using the medial efferent system which, coming from the brainstem, innervates the OHCs.

Adolescent↗