Biomedical subjects

F de Ribaupierre

Publications and source records attributed to F de Ribaupierre.

At least 19 recordsLinked to original sources

PubMed2003

A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss.

Hearing loss can be caused by a variety of insults, including acoustic trauma and exposure to ototoxins, that principally effect the viability of sensory hair cells via the MAP kinase (MAPK) cell death signaling pathway that incorporates c-Jun N-terminal kinase (JNK). We evaluated the otoprotective efficacy of D-JNKI-1, a cell permeable peptide that blocks the MAPK-JNK signal pathway. The experimental studies included organ cultures of neonatal mouse cochlea exposed to an ototoxic drug and cochleae of adult guinea pigs that were exposed to either an ototoxic drug or acoustic trauma. Results obtained from the organ of Corti explants demonstrated that the MAPK-JNK signal pathway is associated with injury and that blocking of this signal pathway prevented apoptosis in areas of aminoglycoside damage. Treatment of the neomycin-exposed organ of Corti explants with D-JNKI-1 completely prevented hair cell death initiated by this ototoxin. Results from in vivo studies showed that direct application of D-JNKI-1 into the scala tympani of the guinea pig cochlea prevented nearly all hair cell death and permanent hearing loss induced by neomycin ototoxicity. Local delivery of D-JNKI-1 also prevented acoustic trauma-induced permanent hearing loss in a dose-dependent manner. These results indicate that the MAPK-JNK signal pathway is involved in both ototoxicity and acoustic trauma-induced hair cell loss and permanent hearing loss. Blocking this signal pathway with D-JNKI-1 is of potential therapeutic value for long-term protection of both the morphological integrity and physiological function of the organ of Corti during times of oxidative stress.

Acoustic Stimulation↗

PubMed2001

Hes1 and Hes5 activities are required for the normal development of the hair cells in the mammalian inner ear.

The mammalian inner ear contains two sensory organs, the cochlea and vestibule. Their sensory neuroepithelia are characterized by a mosaic of hair cells and supporting cells. Cochlear hair cells differentiate in four rows: a single row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs). Recent studies have shown that Math1, a mammalian homolog of Drosophila atonal is a positive regulator of hair cell differentiation. The basic helix-loop-helix (bHLH) genes Hes1 and Hes5 (mammalian hairy and Enhancer-of-split homologs) can influence cell fate determination by acting as negative regulators to inhibit the action of bHLH-positive regulators. We show by using reverse transcription-PCR analysis that Hes1, Hes5, and Math1 are expressed in the developing mouse cochleae. In situ hybridization revealed a widespread expression of Hes1 in the greater epithelial ridge (GER) and in lesser epithelial ridge (LER) regions. Hes5 is predominantly expressed in the LER, in supporting cells, and in a narrow band of cells within the GER. Examination of cochleae from Hes1(-/-) mice showed a significant increase in the number of IHCs, whereas cochleae from Hes5(-/-) mice showed a significant increase in the number of OHCs. In the vestibular system, targeted deletion of Hes1 and to a lesser extent Hes5 lead to formation of supernumerary hair cells in the saccule and utricle. The supernumerary hair cells in the mutant mice showed an upregulation of Math1. These data indicate that Hes1 and Hes5 participate together for the control of inner ear hair cell production, likely through the negative regulation of Math1.

Animals↗

PubMed2000

Spatial expression patterns of epidermal growth factor receptor gene transcripts in the postnatal mammalian cochlea.

Recent in vitro studies demonstrated that members of the epidermal growth factor (EGF) family are involved in hair cell replacement in the postnatal mammalian organ of Corti (OC) after ototoxic damage. This suggests a role for the EGF receptor (EGFR) in this process. We examined the expression of EGFR mRNA within the normal postnatal day 3 (P3) and adult rat cochlear epithelium by RT-PCR and examined its cellular localization with non-radioactive in situ hybridization in P3 and adult cochleae. RT-PCR demonstrated that EGFR mRNA is expressed in P3 and adult cochlear epithelium. In situ hybridization localized high levels of EGFR transcripts in the OC, spiral ganglion, Kölliker's organ and detectable levels in the supporting cells and the stria vascularis of P3 cochlea. In the adult cochlea, EGFR transcripts were detected only in the spiral ganglion. Our results support that the EGFR is implicated in the differentiation of several cochlear cell types and in the response of OC to ototoxic damage of the P3 rat. In the adult, it may participate in the maintenance of the mature neurons and its absence in the OC may contribute to the lack of regenerative responses in the adult cochlea.

Animals↗

PubMed2000

Notch signaling regulates the pattern of auditory hair cell differentiation in mammals.

The development of the mammalian cochlea is an example of patterning in the peripheral nervous system. Sensory hair cells and supporting cells in the cochlea differentiate via regional and cell fate specification. The Notch signaling components shows both distinct and overlapping expression patterns of Notch1 receptor and its ligands Jagged1 (Jag1) and Jagged2 (Jag2) in the developing auditory epithelium of the rat. On embryonic day 16 (E16), many precursor cells within the Kölliker's organ immunostained for the presence of both Notch1 and Jag1, while the area of hair cell precursors did not express either Notch1 and Jag1. During initial events of hair cell differentiation between E18 and birth, Notch1 and Jag1 expression predominated in supporting cells and Jag2 in nascent hair cells. Early after birth, Jag2 expression decreased in hair cells while the pattern of Notch1 expression now included both supporting cells and hair cells. We show that the normal pattern of hair cell differentiation is disrupted by alteration of Notch signaling. A decrease of either Notch1 or Jag1 expression by antisense oligonucleotides in cultures of the developing sensory epithelium resulted in an increase in the number of hair cells. Our data suggest that the Notch1 signaling pathway is involved in a complex interplay between the consequences of different ligand-Notch1 combinations during cochlear morphogenesis and the phases of hair cell differentiation.

Animals↗

PubMed1999

Tissue-specific levels and cellular distribution of epidermal growth factor receptors within control and neomycin-damaged neonatal rat Organ of Corti.

Epidermal growth factor receptor (EGFR) levels were assayed by an enzyme-linked immunosorbent assay (ELISA) in microdissected organ of Corti (OC) from neonatal rats directly after isolation and after 3 days in culture with and without neomycin treatment. In addition, the cellular distribution of the EGFR in the OC was determined by immunohistochemistry. The in vitro level of EGFR determined by ELISA assays doubled after neomycin damage to OC, suggesting that EGFR is subject to up-regulation following this treatment. Immunohistochemistry of both in vivo and in vitro controls indicates that EGFR is predominantly localized in the stereociliary bundles of the hair cells; supporting cells and the apical junctions between the remaining Kolliker organ cells were also immunolabeled. In neomycin-treated cultures, sensory cells were degenerated, so no labeling could be seen. However, supporting and Kolliker organ cells continued to show labeling. In addition, nerve fibers in the region of the future osseous spiral lamina and projecting out toward the damaged sensory epithelium were immunostained. The up-regulation of the EGFR and its redistribution within the OC following neomycin damage support the earlier observation that growth factors that act through EGFR, such as EGF and transforming growth factor-alpha can induce neonatal mammalian auditory hair cell replacement under culture conditions, after aminoglycoside treatment.

Animals↗

PubMed1998

Replacement of mammalian auditory hair cells.

We investigated the potential for hair cell regeneration in neonatal rat organs of Corti grown in culture following destruction of hair cells by neomycin toxicity. Replacement hair cells were observed by light and scanning electron microscopy in lesion sites in the cultures treated with transforming growth factor-alpha, epidermal growth factor or a combination of both factors for 5-7 days post-injury. These new cells had morphological characteristics of immature hair cells. Autoradiographic localization of [3H]thymidine-labelled cells on semi-thin sections indicated that these replacement hair cells did not arise through renewed mitotic division, although an important mitotic proliferation was observed outside the area of supporting and sensory cells.

Animals↗

PubMed1998

Discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus of the rat.

The aim of the present study was to characterize the discharge properties of single neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the rat. In the absence of acoustic stimulation, two types of spontaneous discharge patterns were observed: units tended to fire in a bursting or in a nonbursting mode. The distribution of units in the DNLL based on spontaneous firing rate followed a rostrocaudal gradient: units with high spontaneous rates were most commonly located in the rostral part of the DNLL, whereas in the caudal part units had lower spontaneous discharge rates. The most common response pattern of DNLL units to 200 ms binaural noise bursts contained a prominent onset response followed by a lower but steady-state response and an inhibitory response in the early-off period. Thresholds of response to noise bursts were on average higher for DNLL units than for units recorded in the inferior colliculus under the same experimental conditions. The DNLL units were arranged according to a mediolateral sensitivity gradient with the lowest threshold units in the most lateral part of the nucleus. In the rat, as in other mammals, the most common DNLL binaural input type was an excitatory response to contralateral ear stimulation and inhibitory response to ipsilateral ear stimulation (EI type). Pure tone bursts were in general a more effective stimulus compared to noise bursts. Best frequency (BF) was established for 97 DNLL units and plotted according to their spatial location. The DNLL exhibits a loose tonotopic organization, where there is a concentric pattern with high BF units located in the most dorsal and ventral parts of the DNLL and lower BF units in the middle part of the nucleus.

Acoustic Stimulation↗

PubMed1995

The auditory pathway in cat corpus callosum.

The cortical auditory fields of the two hemispheres are interconnected via the corpus callosum. We have investigated the topographical arrangement of auditory callosal axons in the cat. Following circumscribed biocytin injections in the primary (AI), secondary (AII), anterior (AAF) and posterior (PAF) auditory fields, labelled axons have been found in the posterior two-thirds of the corpus callosum. Callosal axons labelled by small individual cortical injections did not form a tight bundle at the callosal midsagittal plane but spread over as much as one-third of the corpus callosum. Axons originating from different auditory fields were roughly topographically ordered, reflecting to some extent the rostro-caudal position of the field of origin. Axons from AAF crossed on average more rostrally than axons from AI; the latter crossed more rostrally than axons from PAF and AII. Callosal axons originating in a discrete part of the cortex travelled first in a relatively tight bundle to the telo-diencephalic junction and then dispersed progressively. In conclusion, the cat corpus callosum does not contain a sector reserved for auditory axons, nor a strictly topographically ordered auditory pathway. This observation is of relevance to neuropsychological and neuropathological observations in man.

Animals↗

PubMed1995

Morphology and spatial distribution of corticothalamic terminals originating from the cat auditory cortex.

In this paper we studied the morphology and spatial distribution of corticothalamic axons and terminals originating from the auditory cortical fields of the cat. The anterograde tracer biocytin was injected at electrophysiologically characterized loci in the primary (AI) (N = 2), anterior (AAF) (N = 1), posterior (PAF) (N = 1) and secondary (AII) (N = 2) auditory fields. In all cases, two different types of labeled terminals were found in the auditory thalamus: small spherical endings (1-2 microns) and giant, finger-like endings (5-10 microns). After biocytin injections in AI and AAF, the majority of anterogradely labeled axons terminated in the rostral half of the pars lateralis (LV) of the ventral division of the medial geniculate body (vMGB). In LV, the corticothalamic axons ramified profusely, giving rise to dense terminal fields forming well delineated curved stripes, with small spherical endings. Additional terminal fields formed by small endings were observed in the medial division of the medial geniculate body (mMGB). Giant endings were observed in a small area in the dorsal nucleus (D) of the dorsal division of the medial geniculate body (dMGB), near its border with the vMGB. PAF projections were located in the caudal half of vMGB and in mMGB, where only small terminals were found. Giant endings were seen in the superficial part of dMGB emerging from labeled corticothalamic axons oriented in parallel to the dorsal surface of the MGB. Projections from AII gave rise to a main terminal field of small endings in D; a second terminal field consisting of giant endings intermingled with small endings was found in the deep dorsal nucleus (DD) of dMGB. We conclude that small terminals serve the feedback projection to the thalamic nucleus from which the injected cortical field receives its main input, whereas giant terminals cross the borders between the parallel ascending auditory pathways.

Acoustic Stimulation↗

PubMed1994

Changes of single unit activity in the cat's auditory thalamus and cortex associated to different anesthetic conditions.

Single unit spike trains were recorded in the auditory cortex (n = 78) and in the auditory thalamus (n = 55) of nitrous oxide anesthetized cats. The electrophysiological activity was studied before and during the application of pentobarbital (P, 7 mg/kg), ketamine (K, 12 mg/kg) and a mixture of these anesthetics (KP). The units were characterized during the spontaneous and acoustically driven activity ('white' noise and pure tone bursts). For the majority of cortical (61%) and thalamic (83%) units both drugs tended to decrease the spontaneous firing rate, but affected differently its time structure: P tended to increase the average size of burst discharges, whereas K and KP tended to decrease it. In the cortex the peak firing rate evoked by 'white' noise tended to be decreased, whereas stronger excitatory responses were observed in the thalamus after injection of K or KP. The overall effect of the anesthetics during stimulation by pure tones was an increase in tonal selectivity due to a decrease in the response bandwidth. The response pattern to tones was also sometimes affected by the drugs. The direct evidence reported here for significant alterations of the discharge properties of auditory neurons in the thalamus and cortex resulting from low dose administration of K and/or P emphasizes difficulties in comparing data derived from experiments conducted in various conditions of anesthesia or in the awake state.

Acoustic Stimulation↗

PubMed1993

Several neuronal and axonal types form long intrinsic connections in the cat primary auditory cortical field (AI).

Intrinsic connections in the cat primary auditory field (AI) as revealed by injections of Phaseolus vulgaris leucoagglutinin (PHA-L) or biocytin, had an anisotropic and patchy distribution. Neurons, labelled retrogradely with PHA-L were concentrated along a dorsoventral stripe through the injection site and rostral to it; the spread of rostrally located neurons was greater after injections into regions of low rather than high characteristic frequencies. The intensity of retrograde labelling varied from weak and granular to very strong and Golgi-like. Out of 313 Golgi like retrogradely labelled neurons 79.6% were pyramidal, 17.2% multipolar, 2.6% bipolar, and 0.6% bitufted; 13.4% were putatively inhibitory, i.e. aspiny or sparsely spiny multipolar, or bitufted. Individual anterogradely labelled intrinsic axons were reconstructed for distances of 2 to 7 mm. Five main types were distinguished on the basis of the branching pattern and the location of synaptic specialisations. Type 1 axons travelled horizontally within layers II to VI and sent collaterals at regular intervals; boutons were only present in the terminal arborizations of these collaterals. Type 2 axons also travelled horizontally within layers II to VI and had rather short and thin collateral branches; boutons or spine-like protrusions occurred in most parts of the axon. Type 3 axons travelled obliquely through the cortex and formed a single terminal arborization, the only site where boutons were found. Type 4 axons travelled for some distance in layer I; they formed a heterogeneous group as to their collaterals and synaptic specializations. Type 5 axons travelled at the interface between layer VI and the white matter; boutons en passant, spine-like protrusions, and thin short branches with boutons en passant were frequent all along their trajectory. Thus, only some axonal types sustain the patchy pattern of intrinsic connectivity, whereas others are involved in a more diffuse connectivity.

Animals↗

PubMed1991

Auditory corticocortical interconnections in the cat: evidence for parallel and hierarchical arrangement of the auditory cortical areas.

The origin and laminar arrangement of the homolateral and callosal projections to the anterior (AAF), primary (AI), posterior (PAF) and secondary (AII) auditory cortical areas were studied in the cat by means of electrophysiological recording and WGA-HRP tracing techniques. The transcallosal projections to AAF, AI, PAF and AII were principally homotypic since the major source of input was their corresponding area in the contralateral cortex. Heterotypic transcallosal projections to AAF and AI were seen, originating from the contralateral AI and AAF, respectively. PAF received heterotypic commissural projections from the opposite ventroposterior auditory cortical field (VPAF). Heterotypic callosal inputs to AII were rare, originating from AAF and AI. The neurons of origin of the transcallosal connections were located mainly in layers II and III (70-92%), and less frequently in deep layers (V and VI, 8-30%). Single unit recordings provided evidence that both homotypic and heterotypic transcallosal projections connect corresponding frequency regions of the two hemispheres. The regional distribution of the anterogradely labeled terminals indicated that the homotypic and heterotypic auditory transcallosal projections are reciprocal. The present data suggest that the transcallosal auditory interconnections are segregated in 3 major parallel components (AAF-AI, PAF-VPAF and AII), maintaining a segregation between parallel functional channels already established for the thalamocortical auditory interconnections. For the intrahemispheric connections, the analysis of the retrograde tracing data revealed that AAF and AI receive projections from the homolateral cortical areas PAF, VPAF and AII, whose neurons of origin were located mainly in their deep (V and VI) cortical layers. The reciprocal interconnections between the homolateral AAF and AI did not show a preferential laminar arrangement since the neurons of origin were distributed almost evenly in both superficial (II and III) and deep (V and VI) cortical layers. On the contrary, PAF received inputs from the homolateral cortical fields AAF, AI, AII and VPAF, originating predominantly from their superficial (II and III) layers. The homolateral projections reaching AII originated mainly from the superficial layers of AAF and AI, but from the deep layers of VPAF and PAF. The laminar distribution of anterogradely labeled terminal fields, when they were dense enough for a confident identification, was systematically related to the laminar arrangement of neurons of origin of the reciprocal projection: a projection originating from deep layers was associated with a reciprocal projection terminating mainly in layer IV, whereas a projection originating from superficial layers was associated with a reciprocal projection terminating predominantly outside layer IV.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

PubMed1991

Corticofugal modulation of the information processing in the auditory thalamus of the cat.

Single unit activity of 355 cells was recorded in the auditory thalamus of anesthetized cats before, during, and after the inactivation by cooling of the ipsilateral primary auditory cortex (AI). Most of the units (n = 288) showed similar functional characteristics of firing before and after the cryogenic blockade of AI. The spontaneous firing rate remained unchanged by cooling in 20% of the units and decreased in the majority of them (60%). In some regions, i.e. dorsal division of the medial geniculate body (MGB), lateral part of the posterior group of the thalamus, and auditory sector of the reticular nucleus of the thalamus, the maximum firing rate evoked by white noise bursts was generally affected by cooling in the same direction and to the same extent as the spontaneous activity. Units in the ventral division of MGB showed a characteristic increase of signal-to-noise ratio during cortical cooling. The corticofugal modulation led to the appearance or disappearance of the best frequency of tuning in 51 units and changed it by more than 0.5 octave in 34 units. The bandwidths of different response patterns to pure tones stimulation were used to define a set of functional properties. During cryogenic blockade of AI, two cortically modulated sub-populations of units were usually distinguished that exhibited changes for a given functional property. The complexity and diversity of the effects of cortical inactivation suggest that the corticothalamic projection may be the support for selective operations such as an adaptive filtering of the incoming acoustic signal at the thalamic level adjusted as a function of cortical activity.

Acoustic Stimulation↗

PubMed1990

Arborization of corticothalamic axons in the auditory thalamus of the cat: a PHA-L tracing study.

As a result of Phaseolus vulgaris leucoagglutinin (PHA-L) injection in the primary auditory cortex of the cat, portions of corticofugal axons could be traced individually in the reticular complex of the thalamus (RE) and in the medial geniculate body (MGB). On their way to the MGB, axons were seen to give off collaterals which terminated in RE. In the MGB, an individual corticofugal axon was fully reconstructed. It ramified at 3 distinct frontal levels in the rostral half of the pars lateralis (LV). Its terminal branches gave rise to boutons en passant and terminaux in a stripe of LV (parallel to the isofrequency contours), overlapping a cluster of retrogradely labeled neurons, supporting at the microscopic level the principle of the reciprocity of thalamocortical and corticothalamic projections.

Animals↗

PubMed1990

Discharge properties of single units in auditory part of reticular nucleus of thalamus in cat.

1. Extracellular recordings from 153 single units were obtained in the auditory part of the reticular nucleus (RE) of the thalamus of anesthetized cats. 2. In absence of acoustic stimulation, the majority of RE units (75%) had a spontaneous activity characterized by bursts of spikes lasting over 30 ms, alternating with isolated discharges; in contrast, only 30% of units in the medial geniculate body (MGB) showed these long bursts during spontaneous activity. 3. For a majority of RE units (65%), activity evoked by noise bursts consisted in complex response patterns with multiple excitatory and/or inhibitory components. For this stimulus, most units (79%) showed nonmonotonic rate-intensity functions, and median response latency to the first excitatory component was 16 ms, which is slightly longer than that obtained in the anterior part of the ventral division of the MGB for the same conditions. 4. Frequency tuning to pure tones in RE was usually broad: the median value of the width of response ranges was five octaves in RE, as compared to two octaves in the ventral division of the MGB and three octaves in the medial division of the MGB. Responses to tones were complex, usually characterized by frequent changes of response pattern with frequency. No preferential arrangement of units as a function of their best frequency was found along a rostrocaudal or a dorsolateral to ventromedial axis. 5. The present study demonstrates that units in the auditory part of RE have discharge properties clearly different from the main auditory thalamic nucleus, the MGB.

Acoustic Stimulation↗

PubMed1989

Note on the tonotopic organization in the cat medial geniculate body: influence of sampling of units.

The tonotopic organization observed in the present study for the pars lateralis (LV) of the medial geniculate body (MGB) in nitrous oxide anesthetized cats is generally consistent with that previously reported under barbiturate anesthesia. The present data, however, provide evidence for local deviations in characteristic frequency (CF) using appropriate sampling procedures of single units. Although the majority of pairs of units recorded simultaneously with the same microelectrode showed comparable CFs, a few pairs of such neighbouring units displayed CF disparities of up to 1.5 octaves. In addition, some units characterized by an elevated threshold had a CF deviating significantly from the general CF progression observed for the majority of units having low thresholds. This study points out the influence of the sampling procedure on the quality of the tonotopic organization observed in the MGB in addition to a possible effect of the level of anesthesia.

Acoustic Stimulation↗

PubMed1987

Tonotopic organization in the medial geniculate body (MGB) of lightly anesthetized cats.

In the medial geniculate body (MGB) of nitrous oxide anesthetized cats, the pars lateralis (PL) was the only nucleus to show a clear topographic arrangement of its neurons according to their characteristic frequency (CF). When compared to barbiturate anesthetized cats (Imig and Morel 1985a), the tonotopic organization in PL appeared less strict and was characterized by a significant local CF disparity. Furthermore, the degree of tonotopic organization varied along the rostrocaudal axis of the nucleus: it was lower in its caudal than in its rostral half. In the pars ovoidea, the rostral half of the pars magnocellularis (PM) and the suprageniculate nucleus, CF sequences and quantitative evaluations of the tonotopicity indicated the presence of some degree of tonotopic organization which was lower than in PL. No such organization was observed in the caudal part of PM nor in the ventrolateral nucleus, while in the dorsal nucleus, the proportion of tone-responding units was too low for a significant analysis.

Acoustic Stimulation↗

PubMed1987

Functional properties and interactions of neuron pairs simultaneously recorded in the medial geniculate body of the cat.

Pairs of single units were recorded simultaneously from the same microelectrode in the medial geniculate body (MGB) of nitrous oxide anaesthetized cats. Crosscorrelation histograms of each spike train pairs were computed and distributed in five main classes, interpreted in terms of functional interaction between neighbouring neurons. Overall 40% of the 950 recorded pairs showed independent firing during spontaneous activity. Histogram shapes suggestive of simple functional connectivity were found in 38% of the pairs: common inputs (20%), excitatory (15%) and inhibitory (3%) synaptic links. Complex and 'borderline' histogram shapes made up the rest of the sample (22%). Subdivisions of the MGB had the same types and proportions of interaction classes. Several of these interactions showed, in statistical terms only, preferential associations with some other descriptive features of neuronal behaviour: pattern of spontaneous firing, sensitivity to acoustic stimuli, and to a lesser extent characteristic frequency, response latency, response pattern and width of the response range. Simultaneous recording of nearby neuron pairs allowed to test if a given functional property is spatially organized or randomly distributed in the MGB. Response latency, width of the response range behaved as if randomly distributed, whereas binaural interactions and characteristic frequency as if spatially organized.

Acoustic Stimulation↗