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B Canlon

Publications and source records attributed to B Canlon.

At least 19 recordsLinked to original sources
PubMed2005

The signal transduction pathway for the dopamine D1 receptor in the guinea-pig cochlea.

Dopamine released from lateral efferent fibers modulates the activity of the auditory nerve, but the signaling mechanism by which this is mediated is not known. The present study investigated the signal transduction pathway for the dopamine D1 receptor in the guinea-pig cochlea. D1 receptor immunolabeling was localized to the spiral ganglia neurons and at the base of the inner hair cells. Western immunoblotting on whole cochlear preparations revealed positive bands for the D1 receptor and for dopamine and the cyclic AMP-regulated phosphoprotein. The amplitude of the compound action potential was enhanced in the presence of the D1 receptor agonist, SKF 38393, an effect that was abolished by H89, a protein kinase A inhibitor. Conversely, SKF 83566, a D1 receptor antagonist decreased the amplitude of compound action potential, while forskolin, a protein kinase A activator prevented this effect. Furthermore, it was found that the level of glutamate receptor 1 phosphorylation at the protein kinase A site (Ser845) was increased by the D1 agonist, but decreased by D1 antagonist. Our results provide evidence that the D1 receptor is localized in the spiral ganglion neurons as well as the nerve endings under the inner hair cells and they can modulate auditory nerve function. One signal transduction pathway of D1 receptor in the auditory nerve is via protein kinase A-mediated glutamate receptor 1 phosphorylation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2004

The distribution and the modulation of tyrosine hydroxylase immunoreactivity in the lateral olivocochlear system of the guinea-pig.

It was previously shown that tyrosine hydroxylase (TH) immunoreactivity in the terminals of the lateral efferents of the cochlea is decreased by acoustic trauma and that sound preconditioning counteracted this decrease [Hear Res 174 (2002) 124]. Here we identify those neurons in the lateral olivocochlear system (LOC) in the brainstem that regulates the peripheral expression of TH in the cochlea. By employing retrograde tracing techniques, dextran-labeled neurons were found predominantly in the ipsilateral LOC system including lateral superior olive (LSO), and the surrounding periolivary regions (dorsal periolivary nucleus [DPO], dorsolateral periolivary nucleus [DLPO], lateral nucleus of trapezoid body [LNTB]). Employing immunocytochemistry, it was found that a control group had 35% of the ipsilateral LOC neurons positively stained with TH. Of the total population of TH neurons, 77% were double-stained (TH and dextran) in the LOC system. Acoustic trauma decreased the number of TH positive neurons in the LSO and the surrounding DLPO, and caused a reduction of TH fiber immunolabeling in these regions. Changes were not found in the DPO or the LNTB after acoustic trauma. Sound conditioning protected against the decrease of TH immunolabeling by acoustic trauma and increased the fiber staining for TH in the LSO and DLPO, but not in the DPO or the LNTB. These results provide evidence that TH positive neurons are present in the LOC system in the guinea-pig. It is now demonstrated that protection against acoustic trauma by sound conditioning has a central component that is governed by TH in the LSO and the surrounding periolivary DLPO region.

Acoustic Stimulation↗
PubMed2001

The total number of neurons and calcium binding protein positive neurons during aging in the cochlear nucleus of CBA/CaJ mice: a quantitative study.

The quantitative stereological method, the optical fractionator, was used for determining the total number of neurons and the total number of neurons immunostained with parvalbumin, calbindin-D28k (calbindin), and calretinin in the dorsal and posteroventral cochlear nucleus (DCN and PVCN) in CBA/CaJ (CBA) mice during aging (1-39 months old). CBA mice have only a modest sensorineural pathology late in life. An age-related decrease of the total number of neurons was demonstrated in the DCN (r=-0.54, P<0.03), while the total number of neurons in the PVCN did not show any significant age-related differences (r=0.16, P=0.57). In the DCN 5.5% of neurons were parvalbumin positive in the very old (30-39 months) mice, vs. 2.2% in the 1 month old mice. In the DCN 3% of the neurons were calbindin immunopositive in the 30-39 months mice compared to 1.9% in the 1 month old group. In the PVCN, 20% of the neurons in the very old mice were parvalbumin immunopositive, compared to 12% in the young mice. Calbindin did not show any significant age-related differences in the PVCN. The total number of calretinin immunopositive neurons both in the DCN and PVCN did not show any significant change with increasing age. In conclusion, the total neuronal number in the DCN and PVCN was age-related and region-specific. While the neuronal number in the DCN and PVCN was decreased or unchanged, respectively, the calcium binding protein positive neuronal number showed a graded increase during aging in a region-specific and protein-specific manner.

Aging↗
PubMed2001

Short-term adaptation in the peripheral auditory system is related to the AMPA receptor.

The role of glutamate receptors was investigated by infusing N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-isoxazol-propionate (AMPA) into the guinea pig cochlea. Auditory brainstem response thresholds and forward masking were used to determine auditory sensitivity. In the presence of 330 microM NMDA, the auditory brainstem response (ABR) thresholds were elevated by 20-30 dB at 2 kHz and 8 kHz, and the slopes of the forward masking curves were not significantly different from controls. When a high concentration of NMDA (15 mM) was used, ABR thresholds were elevated by 40-50 dB at 2 kHz and 8 kHz and the slopes of the forward masking curves were significantly decreased. In contrast, when AMPA (150 microM) was infused, ABR thresholds were elevated by 20-35 dB at 2 and 8 kHz and the slopes of the forward masking curves were significantly decreased from the control group. When the concentration of AMPA was decreased (100 microM). ABR thresholds were not significantly altered but the slopes of the forward masking curves were significantly decreased from control values. The present study suggests that AMPA receptors play a significantly more important role in short-term adaptation than NMDA receptors.

Adaptation, Physiological↗
PubMed2000

Complementary roles of neurotrophin 3 and a N-methyl-D-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity.

Recent progress has been made regarding the prevention of hearing loss. However, the complete protection of both hair cells and spiral ganglion neurons, with restored function, has not yet been achieved. It has been shown that spiral ganglion neuronal loss can be prevented by neurotrophin 3 (NT3) and hair cell damage by N-methyl-D-aspartate (NMDA) receptor antagonists. Here we demonstrate that the combined treatment with MK801, a NMDA antagonist, and NT3 protect both cochlear morphology and physiology from injury. Pretreatment with MK801 prevented hearing loss and the dendrites of the spiral ganglion neurons from swelling after noise-induced damage. The acute phase of insult with the aminoglycoside antibiotic amikacin resulted in swollen afferent dendrites beneath the inner hair cells. The chronic phase resulted in complete hair cell loss and near-complete loss of spiral ganglion neurons. This damage caused a near-complete loss of hearing sensitivity as displayed by elevated (>90-dB sound pressure levels) auditory brainstem response thresholds. The treatment of amikacin-exposed animals with MK801 gave only a partial protection of hearing. However, the combined treatment with NT3 and MK801 in the amikacin-comprised ear resulted in improved mean hearing within 20 dB of normal. Furthermore, hair cell loss was prevented in these animals and spiral ganglion neurons were completely protected. These results suggest that the NMDA antagonist MK801 protects against noise-induced excitotoxicity in the cochlea whereas the combined treatment of NT3 and MK801 has a potent effect on preserving both auditory physiology and morphology against aminoglycoside toxicity.

Animals↗
PubMed2000

Noise-induced aspartate and glutamate efflux in the guinea pig cochlea and hearing loss.

Aspartate and glutamate were monitored in the scala tympani of the guinea pig cochlea using in vivo microdialysis before and during noise exposure. Moderate level broad band noise [105 dB sound pressure level (SPL), 30 min] neither altered the levels of aspartate or glutamate, nor auditory brainstem response (ABR) thresholds. High level noise exposure (135 dB SPL, 30 min) caused a large increase in aspartate (330%), a smaller increase in glutamate (150%), and a permanent ABR threshold shift of 60-75 dB between 2.0 and 12.5 kHz. Morphological analysis of the cochlea revealed a collapse of supporting structures, swelling of the afferent dendrites under the inner hair cells, and outer hair cell loss. Pretreatment with the NMDA antagonist, MK 801 (1 mg/kg body weight, i.p.) 1 h before noise exposure protected the afferent dendrites from swelling but did not protect the collapse of supporting structures, outer hair cell loss, or auditory thresholds. In conclusion, the noise-induced increase in aspartate and glutamate release in the cochlea and the protective effect of NMDA antagonism suggest that these two neurotransmitters are involved in noise-induced hearing loss.

Acoustic Stimulation↗
PubMed2000

Characterization of hearing in an X,0 'Turner mouse'.

Turner's syndrome is due to total (45,X) or partial (mosaicism) loss of one X-chromosome. The main features are short stature, ovarian dysgenesis with no estrogen production and infertility. In addition to ear and hearing disorders, middle ear problems including acute/serous otitis media and chronic middle ear disease are frequent. Sensorineural hearing loss is often seen with a dip in the mid-frequencies and also an early high frequency loss. In this study, middle-and inner-ear pathology was characterized using physiological and morphological techniques in a 'Turner mouse' that has been generated with the chromosomal aberration X,0. Otitis media was found in some of these X,0 animals, a symptom that is seldom found in control animals. The auditory brainstem responses (ABR) of the Turner mouse showed a progressive hearing loss in the high frequency region that exceeded the normal age-related hearing loss of control mice and increased latencies of the first ABR wave. Outer hair cell loss was apparent in the cochlear basal turn of Turner mice. Decreases in the amplitude of distortion product otoacoustic emissions were correlated with the loss of ABR threshold sensitivity. These results indicate that hearing problems in the Turner mouse seems to be of cochlear origin with an eighth nerve component. This Turner mouse model appears to have ear and hearing problems quite similar to humans and can therefore be used as a model to determine the auditory pathology underlying this syndrome.

Animals↗
PubMed1999

Medial olivocochlear efferent terminals are protected by sound conditioning.

Synaptophysin immunoreactivity was used as a marker for the olivocochlear efferent system that innervates the outer hair cells of the cochlea. An intense noise exposure at either 6.3 kHz or 1.0 kHz caused a significant reduction in anti-synaptophysin immunoreactivity within the 8-6 mm or 14-11 mm distance from the round window, respectively. In the region of the main lesion, the reduction in synaptophysin immunoreactivity for both the 6.3 and 1.0 kHz exposures correlated well with outer hair cell loss. In regions peripheral to the main lesion, some remnants of efferent nerve endings could remain even when their associated outer hair cells were missing. Pre-treatment with a low level sound conditioner (either at 6.3 tone or 1.0 kHz) effectively reduced the efferent and outer hair cell pathology induced by the 6.3 and 1.0 kHz intense noise exposures, respectively. The results demonstrate the feasibility of using anti-synaptophysin immunoreactivity as an effective means of quantifying pathological alterations to the medial cochlear efferent terminals throughout the cochlea. Furthermore, the results show that sound conditioning significantly reduces damage to the efferent terminals.

Acoustic Stimulation↗
PubMed1999

Neurotrophins, NMDA receptors, and nitric oxide in development and protection of the auditory system.

Neurotrophic factors are secreted peptides that when interacting with specific classes of membrane receptors activate intracellular signaling cascades that prevents neuronal death during embryonic development. The establishment of gene-targeted null mutant mice for the neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) has led to the discovery that they are crucial trophic factors for the survival of auditory and vestibular neurons during development. BDNF is the major survival factor for vestibular ganglion neurons, while NT-3 only support a small number of these neurons. In the cochlea, auditory type I neurons require NT3 for their survival, whereas type II neurons depend on BDNF. With this information at hand recent progress has been made regarding the prevention of aminoglycoside-induced hearing loss in the adult guinea pig. These results and the mechanisms leading to hair cell damage are discussed in this paper.

Aminoglycosides↗
PubMed1999

Sound stimulation increases calcium-binding protein immunoreactivity in the inferior colliculus in mice.

The numerical density of calbindin D-28k and parvalbumin immunopositive neurons in the inferior colliculus (IC) in mice was increased after sound stimulation. An increased number of calbindin positive neurons was found in the deep layers of the external cortex (EC) and particularly in the dorsal cortex (DC) and commissural nucleus (NCO). An increase of parvalbumin positive neurons was found in the EC, central nucleus (ICC) and DC, but not in the NCO. The increased immunoreactivity related to sound exposure suggests the appearance of neurons which express these proteins after sound stimulation. The up-regulation of calcium-binding proteins in these neurons may be due to their protective role against overstimulation, their response to a higher auditory metabolic activity, or increasing effect of excitatory inputs after noise-induced hearing loss.

Acoustic Stimulation↗
PubMed1998

Modulating calbindin and parvalbumin immunoreactivity in the cochlear nucleus by moderate noise exposure in mice. . A quantitative study on the dorsal and posteroventral cochlear nucleus.

The number of calbindin D-28k and parvalbumin immunoreactive (IR) neurons were characterized on sections from the cochlear nucleus, dorsal cochlear nucleus (DCN) and posteroventral cochlear nucleus (PVCN) using two-dimensional quantification. After noise exposure (6-12 kHz, 2 h, at either 80 dB SPL or 103 dB SPL), the number of calbindin and parvalbumin immunoreactive neurons increased in CBA/CBA mice. Quantitative analysis of calbindin-IR in the PVCN did not show a statistically significant difference between any of the groups, whereas statistically significant differences in calbindin-IR were found in the DCN for the 103 dB and 80 dB group compared to the control group, and 103 dB compared to the 80 dB group, respectively. A statistically significant increase in the number of parvalbumin-IR neurons in the PVCN and the DCN was evident in the 103 dB and 80 dB group compared to the control group, and in the 103 dB compared to the 80 dB group. The data indicate that increasing sound stimulation causes a graded increase in the expression of calcium-binding protein immunoreactivity in the DCN and PVCN neurons and neuropil. This increase of protein expression is due to increased positive immunoreactivity in 'silent' neurons. These findings implicate that these neurons have the possibility to react against trauma and display calbindin or parvalbumin as a rescue event. The ability to map sound-induced calcium-binding protein changes in auditory neurons may be useful in future studies designed for detecting early patterns of neurodegeneration and neuroprotection in the central auditory pathway.

Acoustic Stimulation↗
PubMed1998

Reducing noise damage by using a mid-frequency sound conditioning stimulus.

Sound conditioning guinea pigs to a 6.3 kHz tone at 78 dB SPL for either 13 or 24 days provides significant physiological (auditory brain stem responses, ABR; and distortion product otoacoustic emissions, DPOAE) and morphological (cochleograms) protection against a subsequent traumatic exposure (6.3 kHz, 100 dB SPL for 24 h) delivered 2 h after sound conditioning. Threshold shifts (ABR, DPOAE) were significantly reduced and the degree of hair cell loss was minimal. When a 1 week pause was given between the end of the sound conditioning and the traumatic exposure, protection was still observed, but to a lesser degree. These findings demonstrate that mid-frequency sound conditioning protects against noise trauma and that the protective effect is maintained for at least 1 week.

Acoustic Stimulation↗
PubMed1998

Receptor potential characteristics during direct stereocilia stimulation of isolated outer hair cells from the guinea-pig.

The receptor potential as a function of stimulus amplitude and frequency was studied with the patch-clamp technique in isolated outer hair cells (OHCs) with a length ranging from 30 to 87 microm during direct mechanical stimulation of the stereocilia. The amplitude and frequency of the stimulation were varied from 125 nm to 2 microm and from 100 Hz to 2.5 kHz, respectively. The mean resting membrane potential before stimulation was -64.25 +/- 1.4 mV (mean +/- SE, n = 26). Irrespective of the frequency used, stereocilia stimulation produced a combination of AC and DC responses, and both components showed saturation with increasing stimulation. Frequency responses appeared to be a function of intensity and resembled a low-pass filter with a time constant ranging from 0.2 to 2.0 ms. With increasing stereocilia stimulation, the relative contribution of high frequencies to the AC component decreased, suggesting a decrease of the corner frequency. The saturated amplitude of the AC component for low-frequency stimulation (100 Hz) was proportional to cell length and increased with a mean rate of 0.014 mV microm(-1). A relationship between the DC response of the receptor potential and the pre-stimulus membrane potential was found. Recordings with more negative membrane potentials had greater DC components, while more depolarized recordings demonstrated smaller DC components. These fluctuations seemed to be defined by the interaction between the probe and stereocilia bundle and could be in the range of the transfer function for each cell.

Animals↗
PubMed1997

The effect of stereocilia bundle position on receptor potential characteristics of isolated outer hair cells in the guinea pig.

The receptor potential as a function of pre-stimulus position of the stereocilia was studied with the whole cell patch-clamp technique in isolated outer hair cells (OHC) during direct mechanical stimulation of the stereocilia (n = 6, cells ranging from 70-87 microm length). The amplitude and frequency of the stimulation was 1 microm and 100 Hz. Controlled pre-stimulus stereocilia displacements in the excitatory direction were followed by sustained membrane depolarization and a diminution of the DC component of the receptor potential. Spectral analysis has shown that recordings with most diminished DC components had a pronounced fundamental while the other harmonics were suppressed, indicating the linearization of the receptor potential. The observed non-lineararities depended on the resting position of the stereocilia and seemed to be determined by the operating range of the transduction process.

Analysis of Variance↗
PubMed1997

Pattern of synaptophysin immunoreactivity in the efferent nerve terminals of the guinea pig cochlea.

The goal of the present study was to analyze the distribution of efferent 8th nerve synaptic endings in a surface preparation of the guinea pig cochlea using synaptophysin antibodies. Employing light and confocal microscopy synaptophysin immunoreactivity was found exclusively at the base of the outer hair cells (OHCs) and the inner hair cells (IHCs) axosomatic efferent synapses. Qualitative and quantitative differences were found between the OHCs and the IHCs immunoreactivity. Efferent nerve endings innervating IHCs were comparatively smaller, more numerous and densely packed. Efferent terminals demonstrated a longitudinal gradient for the IHCs and a longitudinal and radial gradient for the OHCs. Quantitative analysis of synaptophysin immunofluorescence demonstrated a higher percentage of efferent terminals innervating the IHCs and the OHCs in the mid and basal segments of the cochlea than in the apical regions. In addition, a radial gradient from the 1st to 3rd row of OHCs was evident. The results from the present study show that the analysis of synaptophysin immunoreactivity on cochlear surface preparations allows the efferent innervation to be determined throughout the entire cochlea. This technique allows for a rapid assessment of the normal cochlea as well as after cochlear insult.

Animals↗
PubMed1997

The effect of repeated daily noise exposure on sound-conditioned and unconditioned guinea pigs.

Sound-conditioned and unconditioned guinea pigs were exposed every day for 10 consecutive days to noise exposure resulting in a temporary threshold shift (2767 Hz, 103 dB SPL, 5 min). The cubic distortion product otoacoustic emissions (DPOAE) were followed at a constant L1 intensity of 60 dB SPL at 1.75, 2.8, 3.5, and 4.4 kHz for 90 min post-exposure. Four parameters (area under the curve, duration of loss, maximal loss, and time point for maximal threshold shift) were analyzed to determine the effect of repeated daily noise exposure for each group. The sound-conditioned group (1) was significantly less affected by overstimulation during the initial days of exposure compared to the unconditioned group and (2) gradually became more affected by overstimulation as the daily sessions progressed. The 'training effect' induced by sound conditioning gradually deteriorated after approximately 5 or 6 days of repeated stimulation. However, at day 10 the sound-conditioned group never had emissions that were worse than day 1 overstimulation for the unconditioned group. The unconditioned group, on the other hand, illustrated significantly greater threshold shifts during the initial days of overexposure and then demonstrated a gradual resistance to overstimulation during subsequent days.

Adaptation, Physiological↗
PubMed1997

Protection against noise trauma by sound conditioning.

Sound conditioning provides protection against a subsequent noise trauma. The sound conditioning paradigm consists of a low-level, long-term, non-damaging acoustic stimulus (1 kHz, 81 dB SPL x 24 days). Morphological and physiological alterations are not induced by the sound conditioning stimulus alone. In addition, the middle ear muscles have been shown not to be influenced by sound conditioning. It has been shown that after exposure to a traumatic stimulus, sound conditioning protects the outer hair cell morphology (fewer missing outer hair cells), as well as physiology (distortion product otoacoustic emissions) compared to an unconditioned group exposed only to the traumatic stimulus. Further studies are needed in order to establish the underlying mechanisms for the phenomenon of sound conditioning. Nevertheless, since sound-conditioning experiments have been successfully applied to human subjects our understanding of hearing impaired individuals has been enhanced.

Adaptation, Physiological↗