Biomedical subjects

E W Rubel

Publications and source records attributed to E W Rubel.

At least 73 records · Page 4Linked to original sources

PubMed1995

Protein masking of a ribosomal RNA epitope is an early event in afferent deprivation-induced neuronal death.

Cell death in the developing nervous system is regulated by both afferent synaptic activity and target-derived neurotrophic factors. Loss of afferent innervation via unilateral cochlea removal results in the death of 20-40% of neurons in the neonatal chick cochlear nucleus, nucleus magnocellularis (NM). The process of NM neuronal death involves structural and functional alterations in ribosomes, including decreased protein synthesis, loss of immunoreactivity for a monoclonal anti-ribosomal RNA (rRNA) antibody, Y10B, and eventual ribosome degradation. In the present report we confirm that the Y10B antibody binds specifically to ribosomes in chick NM neurons by electron microscopy. We then performed experiments designed to determine whether loss of rRNA immunoreactivity observed in NM neurons following cochlea removal involves induction of a protein-rRNA interaction. Brain stem tissue from animals subjected to unilateral cochlea removal was treated with protease prior to immunolabeling. Protease treatment restored rRNA immunoreactivity after 3 h of afferent deprivation, confirming that afferent deprivation induces protein-rRNA interactions which mask the Y10B epitope. Immunoprecipitation experiments confirmed that the Y10B antibody recognizes a specific rRNA sequence without posttranscriptional modification.

Afferent Pathways↗

PubMed1995

Hair cell replacement in avian vestibular epithelium: supporting cell to type I hair cell.

Previous investigations have demonstrated that the sensory epithelium of the avian vestibular system possesses the capacity to replace hair cells both on an ongoing basis and following severe damage. Supporting cells, within the sensory epithelium, are believed to be the progenitors of the regenerated hair cells. In the present study we describe the series of events leading to the formation of a regenerated vestibular hair cell in post-hatched birds. Young chickens received injections of streptomycin sulfate in order to damage the sensory epithelium of the vestibular system. These injections were followed by injections of the cell proliferation marker tritiated-thymidine. At predetermined intervals, the animals were killed, and the vestibular organs were processed for tissue autoradiography. Our results confirm that hair cells originate from supporting cells. The data also indicate that postmitotic cells migrate towards the lumen of the epithelium where they differentiate into Type II hair cells. At a later time, some of the new Type II hair cells further differentiate into Type I hair cells. These results suggest that both types of avian vestibular hair cells have a common ancestor. The data also provide evidence in support of the hypothesis that calyx enclosed Type I hair cells, only present in birds and mammals, are a more differentiated stage of Type II hair cells.

Animals↗

PubMed1995

Regenerated hair cells in the European starling: are they more resistant to kanamycin ototoxicity than original hair cells?

Previous work from our laboratory [Marean et al. (1993) Hear. Res. 71, 125-136] has shown that a 10 day dose of 200 mg/kg/day kanamycin produced damage to the basal 34% of the starling basilar papilla. We also observed that repeating the dosing schedule following a 4 month survival period resulted in significantly less damage to the regenerated auditory epithelium. The present study investigated whether or not this apparent resistance was the result of a tendency for regenerated hair cells to be less susceptible to kanamycin ototoxicity, or if other, systemic factors may be involved. Eight European starlings were given subcutaneous injections of 200 mg/kg/day kanamycin for 10 days. Serum levels of kanamycin were measured at the time of sacrifice for all birds, and the basilar papillae of all birds were examined by scanning electron microscopy (SEM). Two of these birds (Group 1) were sacrificed immediately following the dosing period. Two of the birds were allowed to survive for 60 days (Group 2). Two of the birds were redosed with 200 mg/kg/day for 10 days after 60 days survival (Group 3). Finally, two birds were redosed with 250 mg/kg/day until serum levels of kanamycin were the same as Group 1 when sacrificed (> 9 micrograms/ml). The SEM results showed that the regenerated auditory epithelium of the birds dosed a second time sustained less damage compared to previously untreated ears, even though the dosing regimen was the same (Group 3 versus Group 1). The regenerated auditory epithelium of birds dosed a second time sustained the same damage as previously untreated animals when the dosage was increased to attain similar serum levels (Group 4 versus Group 1). These results suggest metabolic changes occur in the starling in response to the initial dose of kanamycin which do not necessarily involve changes in hair cell resistance to ototoxicity.

Animals↗

PubMed1995

Acoustic features and acoustic changes are represented by different central pathways.

The central processing of acoustic stimulus changes can be observed neurophysiologically in the mismatch negativity auditory evoked potential (MMN). Stimuli differing in interaural phase were used to investigate the contributions of the primary and non-primary auditory pathways to the encoding of binaural stimuli and to investigate passively elicited measures of binaural processing in experimental animals. In guinea pigs, the MMN was obtained in response to 1000 Hz tones embedded in white noise (S:N = 2 dB). Using a modified oddball paradigm (that is, two stimuli presented in a series, each with a different probability of occurrence), stimuli were presented binaurally with both the tone and noise in-phase to the two ears (S0N0) as the standard stimulus ans the tone 180 degrees out-of-phase (S(PI)N0) as the deviant stimulus. The MMN, by definition, should occur only in response to a change, or 'mismatch,' between the standard and deviant stimuli. The response to the deviant stimulus in the oddball paradigm was compared to the response to the same stimulus when presented in a series alone. The responses to S0N0 and S(PI)N0 collected in a series alone, termed the intrinsic responses, were also compared. Responses were recorded from two surface epidural electrodes - one at the posterior midline and one over the left temporal lobe. AEPs from these locations have been shown to reflect the activity of primary and non-primary thalamo-cortical pathways respectively. A significant MMN was observed at the midline electrode, but no MMN was observed over the temporal lobe.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1995

Effects of middle ear pressure on frequency representation in the central auditory system.

Changes in middle ear pressure (MEP) are known to produce an attenuation of sound transmission through the outer and middle ear, but the effects on frequency representation in the auditory system have not previously been studied. This issue is of particular interest because of changes in MEP occurring during episodes of otitis media. We have investigated the effect of changes in MEP on the tuning of neurons in the inferior colliculus (IC) of the gerbil to calibrated tone stimulation of the contralateral, pressurized ear. Both negative and positive non-atmospheric MEP produced an elevation of neural thresholds that was inversely related to IC neuron best frequency (BF). A robust, linear relationship was found between BF at atmospheric MEP (control) and BF at -20 daPa MEP. Higher resolution analysis was performed on a sub-sample of neurons that had particularly stable BFs with repeated, control MEP. For the majority of these neurons, alternation of MEP between control and -20 daPa had no effect on BF. However, a few neurons showed small (up to 5%), significant shifts in BF with -20 daPa MEP. These results are consistent with previous reports of the effects of MEP on spontaneous otoacoustic emissions. We conclude that non-atmospheric MEP acts as a high-pass filter on the input to the cochlea, but does not change the frequency organization of the auditory system to any marked extent.

Acoustic Stimulation↗

PubMed1995

Avian cochlear hair cell regeneration: stereological analyses of damage and recovery from a single high dose of gentamicin.

Hair cell regeneration after acoustic trauma has been conclusively documented in birds. Previous studies of aminoglycoside ototoxicity have typically used 5-10 day courses of drug to damage the cochlea and trigger regeneration. This long-term lesion prevented analysis of the early events of regeneration. We set out to determine how much damage would occur and how recovery would proceed after a single high-dose injection of the aminoglycoside gentamicin. White Leghorn chicks were given a single high dose of gentamicin (100 mg/kg). Three post-injection survival groups with age-matched controls were studied: short-term (3-5 days), intermediate-term (2 weeks) and long-term (5 weeks). After sacrifice, cochleae were dissected and processed for scanning electron microscopy. Using stereological techniques, a quantitative analysis of cochlear hair cell counts along the proximal 50% of the cochlea was performed from scanning electron micrographs on 4-7 chicks from each group. Variable degrees of damage were seen 3-5 days after the drug injection. All hair cells were lost from the proximal 20% of the cochlea in all chicks. This complete hair cell loss could extend to 50% of the cochlea. Immature appearing hair cells could be first identified by their immature stereocilia at 3 days. Immature appearing hair cells were present in greatest number in regions which had been denuded of native hair cells and in regions where partial loss occurred. Interestingly, immature appearing hair cells also occasionally appeared in adjacent areas in which there was no apparent loss of native hair cells. Two-week survivors showed an elevation in hair cell number compared to controls in regions which had sustained damage and immediately adjacent regions. This elevation implies that an overproduction of hair cells might occur as part of the regeneration response. By 5 weeks after damage hair cell numbers approximated controls.

Animals↗

PubMed1995

Effects of furosemide on distortion product otoacoustic emissions and on neuronal responses in the anteroventral cochlear nucleus.

1. The objective of this study was to precisely evaluate the relationship between the threshold of neurons in the anteroventral cochlear nucleus (AVCN) and the properties of distortion product otoacoustic emissions (DPOAEs). Response areas of multiunit clusters in the AVCN and DPOAEs in the ear canal were measured alternately in the adult gerbil during furosemide-induced changes of the endocochlear potential. Stimulus frequencies of the probe tones for DPOAE measurement were in the range of f1 = 1.7-7.6 kHz and f2 = 2.0-9.0 kHz; the ratio f2:f1 was always 1.18. Stimulus amplitudes were varied in 5-dB steps from 30 to 80 dB SPL, with either equal amplitudes (L1 = L2) or unequal, with L1 set 10 dB above L2. Multiunit response areas were determined from cluster responses to a series of 100-ms tone bursts presented with a pseudo-random sequence in frequency and intensity. 2. Changes in the multiunit discharge properties after 50-75 mg/kg furosemide injection were as follows: the best frequency (BF) threshold increased from initial values in the range of 20-30 dB SPL to 50-80 dB SPL at 10-20 min postinjection and then recovered fully by 60-90 min. The spontaneous discharge activity decreased to zero before any changes in the frequency threshold curve were observed and did not return to initial values for several hours. Likewise, total discharge rates of stimulus elicited responses were reduced and tended to stay reduced even after BF threshold had fully recovered. 3. From the DPOAE measurements, the changes observed in the cubic distortion tone (CDT, 2f1-f2) emission after furosemide injection were as follows: at high levels of the probe tones, changes in the emission intensities generally stayed within a 10-dB range. The CDT amplitudes for low stimulus levels, however, were typically reduced by up to 40 dB, but recovered (depending on the furosemide dosage) by approximately 60-90 min. 4. At low to moderate stimulus levels of 40-60 dB SPL, there was a near perfect, minute-by-minute covariation of the ear canal CDT amplitude and the BF threshold measured in the AVCN. A 10-dB increase in threshold was associated with a 5- to 7-dB decrease in the CDT emission. 5. The optimum stimulus parameter set for the noninvasive estimation of cochlear performance from the CDT response was for stimulus amplitudes L1 = 50, L2 = 40 dB SPL. 6. This experiment demonstrates that CDT emissions at low stimulus levels are very good predictors of the thresholds of cochlear afferents, but this validity is lost for BF thresholds greater than approximately 60-70 dB SPL. 7. The ear canal CDT amplitude is better correlated with the BF threshold sensitivity of neuronal response areas in the AVCN than with the spontaneous discharge rate or absolute above-threshold discharge rates.

Animals↗

PubMed1995

Mitochondrial role in hair cell survival after injury.

The role of mitochondrial biogenesis in hair cell survival after injury was evaluated by inhibiting mitochondrial protein synthesis with chloramphenicol and then studying the effects on hair cell survival after exposure to two different types of ototoxins, gentamicin and acoustic trauma. Seven- to 10-day-old chicks were treated with either a single injection of gentamicin (250 mg/kg) or noise (1500 Hz at 120 dB sound pressure level for 14 hours). A subset of the gentamicin- and noise-treated animals also received chloramphenicol (1200 mg/kg during a 24-hour period) through a subcutaneous osmotic pump. A control group received chloramphenicol alone (1200 mg/kg during a 24-hour period). All animals were sacrificed after 5 days, and their basilar papillae (cochleas) were prepared for scanning electron microscopy. Hair cell loss was quantified with stereologic techniques. Animals treated with chloramphenicol alone did not have any evidence of hair cell loss. Gentamicin-treated animals had characteristic hair cell loss beginning at the basal tip and tapering out along the inferior edge more distally. The addition of chloramphenicol to gentamicin treatment significantly increased hair cell loss by 30%, extending the area of hair cell loss into the superior hair cell region at the distal boundary of the lesion. Pure-tone noise exposure characteristically produced hair cell loss along the inferior edge and occasionally included hair cells along the most superior edge. Addition of chloramphenicol to noise exposure significantly increased hair cell loss by 80%, with extension of the lesion across the full width of the sensory epithelium and basally. These results demonstrate that mitochondrial biogenesis is involved in cellular responses to injury. They suggest that mitochondrial function may regulate the probability of survival after metabolic challenges to hair cell integrity.

Animals↗

PubMed1995

Cell cycle progression in gentamicin-damaged avian cochleas.

Hair cells, the sensory receptors of the auditory, vestibular, and lateral-line organs, may be damaged by a number of agents including aminoglycoside antibiotics and severe overstimulation. In the avian cochlea, lost hair cells can be replaced by regeneration. These new hair cells appear to be derived from a support cell precursor which is stimulated to divide by events associated with hair cell loss. Little is known about the timing and sequencing of events leading to new hair cell production. In this study cell cycle-associated events in the avian cochlea were analyzed at early and late time intervals following a single high dose of gentamicin. This single dose protocol has been shown to consistently result in extensive morphological damage and hair cell loss in the proximal region of the cochlea while sparing a morphologically undamaged distal cochlear region. This allowed for the differential analysis of the underlying support cell populations with respect to local hair cell loss. Three cell cycle associated markers were used to evaluate which cells entered and progressed through the cell cycle: statin, a G0 associated nuclear marker; proliferating cell nuclear antigen (PCNA), a G1, S and G2 associated marker; and 5-bromodeoxyuridine (BrdU), an S phase associated marker. Using these markers we found evidence for reversible changes in cell cycle status throughout the cochlea, while progression through S phase and mitosis was restricted to the region of the cochlea which sustained hair cell loss.

Aging↗

PubMed1995

Activation of a metabotropic glutamate receptor increases intracellular calcium concentrations in neurons of the avian cochlear nucleus.

Metabotropic glutamate receptors have been shown to stimulate phosphatidylinositol metabolism, and subsequently liberate Ca2+ from intracellular stores, in a variety of tissue and cell types. We previously demonstrated that glutamate could stimulate phosphatidylinositol metabolism, generating inositol-1,4,5-trisphosphate (IP3), in isolated cochlear nucleus tissue from the chick. Using the calcium indicator dye fura-2 and ratiometric fluorescent imaging, this study examined the ability of glutamate and its analogs to liberate Ca2+ from intracellular stores of neurons of the avian cochlear nucleus, and qualitatively characterized the pharmacological profile of such an action. In normal, Ca(2+)-containing medium, glutamate, kainate (KA), alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), NMDA, quisqualate (QUIS), and (+/-)-aminocyclopentane-trans-dicarboxylate (ACPD) elicited increases in intracellular calcium concentrations ([Ca2+]i). In the absence of external Ca2+, glutamate, quisqualate, and ACPD evoked increases in [Ca2+]i. In normal medium, the ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV) attenuated but did not abolish the glutamate-evoked response and had no effect on the ACPD-evoked response. The putative metabotropic glutamate receptor antagonist 2-amino-3-phosphonopropionate (AP3) was without effect on the glutamate- and ACPD-evoked increases in [Ca2+]i in Ca(2+)-free medium. We conclude that a metabotropic glutamate receptor (mGluR) is present on cochlear nucleus neurons and is able to stimulate the phosphatidylinositol metabolism--Ca2+ signal transduction cascade.

Animals↗

PubMed1995

Glutamatergic inhibition of voltage-operated calcium channels in the avian cochlear nucleus.

The auditory nerve serves as the only excitatory input to neurons in the avian cochlear nucleus, nucleus magnocellularis (NM). NM neurons in immature animals are dependent upon auditory nerve signals; when deprived of them, many NM neurons die, and the rest atrophy. Auditory nerve terminals release glutamate, which can stimulate second messenger systems by activating a metabotropic glutamate receptor (mGluR). Therefore, it is possible that the effectors of mGluR-stimulated signal transduction systems are needed for NM neuronal survival. This study shows that mGluR activation in NM neurons attenuates voltage-dependent changes in [Ca2+]j. Voltage-dependent Ca2+ influx was also attenuated by increasing cAMP with forskolin, VIP, or 8-bromo-cAMP, indicating that mGluR activation may stimulate adenylate cyclase. The main results may be summarized as follows. NM neurons possess high voltage-activated Ca2+ channels that were modulated by quisqualate, glutamate, and (+/-)trans-ACPD, in that order of potency. Glutamatergic inhibition of Ca2+ influx was not blocked by L-AP3 or L-AP4, which antagonize the actions of mGluRs in other neural systems; it was blocked by serine-O-phosphate. Finally, the attenuation of voltage-dependent Ca2+ influx was duplicated by cAMP accumulators. Since NM neurons have high rates of spontaneous activity and higher rates of driven activity, the expression of this mGluR turns out to be very valuable: without it, [Ca2+]j could reach lethal concentrations. These results provide an important clue as to the identity of an intracellular signal that may play an important role in NM neuronal survival.

Animals↗

PubMed1994

Reduced retinal activity increases GFAP immunoreactivity in rat lateral geniculate nucleus.

Dynamic regulation of astrocytic processes by the electrical activity of local neurons has been previously described in chick cochlear nucleus. The present study extends this observation by showing that astrocytes in the rat lateral geniculate nucleus (LGN) also increase their immunoreactivity for glial fibrillary acidic protein (GFAP) soon after deprivation of afferent visual neuronal activity. Within 6 h of enucleation, which eliminates a major source of afferent input to the contralateral LGN, GFAP immunoreactivity increases relative to the ipsilateral LGN. A similar increase in GFAP immunoreactivity can be induced by intraocular injections of tetrodotoxin, demonstrating that a reversible manipulation of optic nerve electrical activity is sufficient to regulate LGN astrocytes. This rapid response to activity deprivation is less dramatic than the gliotic reaction observed 3 weeks following deafferentation, by which time afferent terminals have degenerated. These results support the notion that regulation of astrocytic processes by neural activity may play an important role in activity-dependent synaptic regulations in the various sensory systems of vertebrates.

Animals↗

PubMed1994

Identification and purification of a chicken brain neuroglia-associated protein.

The identification, purification, and biochemical characterization of specific markers for neuroglial cells in the central nervous system is an essential step toward a better understanding of the function of glial cells. This manuscript reports the identification and purification of a neuroglia-associated protein (NAP-185) with an apparent molecular mass of 185 kDa. While its expression is not restricted to the brain, it was first identified in a specific subpopulation of glial cells when chick brain stem sections were analyzed with an affinity-purified rabbit antiserum raised against the catalytic domain of the T-cell protein tyrosine phosphatase. This 185-kDa antigen was purified to apparent homogeneity and confirmed to be responsible for the neuroglial staining observed. In spite of its immunological relation to T-cell protein tyrosine phosphatase, purified NAP-185 failed to display tyrosine phosphatase activity. The primary sequence of five NAP-185-derived peptides shows that this protein has not yet been characterized and that it is possibly related to AP180, a clathrin-associated protein.

Amino Acid Sequence↗

PubMed1994

GABAergic terminals in nucleus magnocellularis and laminaris originate from the superior olivary nucleus.

The auditory brainstem nuclei, angularis (NA), magnocellularis (NM), and laminaris (NL) of the chicken, Gallus, contain terminals that stain for antibodies against the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). Some of these terminals originate from cells surrounding nucleus magnocellularis. Results from this study indicate that the majority of the GABAergic terminals found in NA, NM and NL originate from the superior olivary nucleus (SON). Injections of cholera toxin and horseradish peroxidase show that superior olivary nucleus (SON) neurons, which respond to pure tones, project bilaterally to NA, NM, and NL. NA and NL are reciprocally connected with the SON. More NA cells project to the SON than NL cells. While SON neurons project to NM, NM neurons do not project axons back to the SON. The configuration of SON terminals in NA, NM and NL matches the pattern of GABA-immunoreactive puncta seen in these three nuclei: they surround individual NM cells, congregate in the dendritic neuropil of NL, and blanket the NA. The data indicate that NA, NM and NL may be affected by two different inhibitory cell types: local interneurons and SON neurons. Patterns of connectivity described in this report suggest that the activity of NA cells could influence NM and NL cell physiology. Specifically, increases in NA cell activity could augment the effects of GABAergic SON neurons on NM and NL. Hence, binaural perception in the chicken may be more dependent upon changes in intensity cues than previously believed.

Acoustic Stimulation↗

PubMed1994

Effect of altered neuronal activity on cell size in the medial nucleus of the trapezoid body and ventral cochlear nucleus of the gerbil.

Activity-dependent transneuronal regulation of neuronal soma size has been studied in the medial nucleus of the trapezoid body and ventral cochlear nucleus of adolescent gerbils. Cochlear ablation or tetrodotoxin has been used to eliminate afferent electrical activity in auditory nerve fibers permanently or for 24 or 48 hours. Previous studies have shown that the cross-sectional area of spherical cell somata in the ipsilateral anteroventral cochlear nucleus decreases within 24 hours of electrical activity blockade with tetrodotoxin, which is fully reversible when activity is restored. The present findings extend this work by directly comparing the results of unilateral blockade of auditory nerve action potentials or unilateral cochlear ablation on the size of spherical and globular cell bodies in the ventral cochlear nucleus with changes produced by the same manipulations in third-order cells, principal neurons in the medial nucleus of the trapezoid body. Soma size in both ventral cochlear nucleus cell types decreases reliably by 24 hours after cochlear removal or eighth nerve activity blockade by tetrodotoxin. Soma size of neurons in the contralateral medial nucleus of the trapezoid body decreases 48 hours, but not 24 hours, after either manipulation. When activity in auditory nerve fibers is allowed to resume for 7 days following a 48-hour activity blockade, soma size fully recovers in the medial nucleus of the trapezoid body as well as in ventral cochlear nucleus neurons. We also report that the cross-sectional area of neuronal soma in the medial nucleus of the trapezoid body is larger in lateral regions of medial nucleus of the trapezoid body (low-frequency representation) than in the medial regions of the nucleus (high-frequency representation). We conclude that cell body size changes in brainstem auditory neurons are reversible and that the signals associated with the loss and subsequent recovery of soma size are activity related. However, the delayed effect of activity deprivation in the medial nucleus of the trapezoid body suggests that trophic substances released by afferent axons may contribute to the maintenance of anatomical characteristics.

Action Potentials↗

PubMed1994

Astrocyte proliferation in the chick auditory brainstem following cochlea removal.

Astrocytes in the central nervous system (CNS) respond to injury and disease by proliferating and extending processes. The intermediate filament protein of astrocytes, glial fibrillary acidic protein (GFAP) also increases in astrocytes. These cells are called "reactive astrocytes" and are thought to play a role in CNS repair. We have previously demonstrated rapid increases (< 6 hours) in GFAP-immunoreactive and silver-impregnated glial processes in the chick cochlear nucleus, nucleus magnocellularis (NM), following cochlea removal or activity blockade of the eighth nerve. It was not known whether these changes were the result of glial proliferation, glial hypertrophy, or both. The present study examined the time course of astrocyte proliferation in NM following cochlea removal. Postnatal chicks received unilateral cochlea removal and survived for 6, 12, 18, 24, 36, 48, and 72 hours. Bromodeoxyuridine was used to label proliferating cells. The volume and number of labeled cells in NM was calculated for both the experimental and control sides of the brains for experimental animals was well as for unoperated control animals. A subset of astrocytes continuously divide in the normal posthatch chick brainstem. The percentage of labeled nuclei increases within NM 36 hours following cochlea removal and is robust by 48 hours. This increase is due to astrocyte proliferation within, rather than migration to, NM. These results indicate that rapid increases in GFAP following reduced activity are independent of cell proliferation. The time course of astrocyte proliferation suggests that cellular degeneration within the nucleus may play a role in upregulating astrocyte proliferation.

Animals↗

PubMed1994

Variation of distortion product otoacoustic emissions with furosemide injection.

Cochlear function was monitored in adult gerbils using distortion product otoacoustic emissions (DPOAE) during intraperitoneal injection of furosemide. All stimulus parameters were varied independently over a wide range, the stimulus frequencies f1 and f2 from 1 to 16 kHz, and the stimulus levels L1 and L2 from 20 to 80 dB SPL. The observed emissions at 2f1-f2 and 3f1-2f2 could be considered to be made up of two distinct components: (1) an 'active' source which depended in a complex way on the stimulus frequencies and levels, which was dominant at low and moderate stimulus levels, and which, by definition, was eliminated by sufficient furosemide intoxication; and (2) a 'passive' source which was essentially the same at all frequencies, with a level dependence given approximately by a simple power law distribution. The change from the active to the passive source was usually accompanied by an abrupt shift in emission phase angle. A simple summation model was shown to account for the observed form of this transition. The amount of the decrease in 2f1-f2 emission amplitude after furosemide injection was approximately independent of frequency and consistent for the middle frequency ratios and intensity levels (f2/f1 approximately equal to 1.3, L1 x L2 approximately equal to 55 x 50 dB SPL). It was concluded that the combination of DPOAE with furosemide injection can usefully be employed as a probe of active cochlear mechanics.

Acoustic Stimulation↗

PubMed1994

Glutamate-stimulated phosphatidylinositol metabolism in the avian cochlear nucleus.

This study examined the ability of the excitatory amino acid glutamate and its analogs to stimulate phosphatidylinositol metabolism in isolated cochlear nucleus tissue from young chicks. In the presence of lithium chloride, glutamate and (+/-)-1-aminocyclopentyl-trans-1,3-dicarboxylate (ACPD) stimulated the formation of inositol phosphates to levels significantly above unstimulated control levels. Unexpectedly, quisqualate did not stimulate inositol phosphates formation. The N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV), the ionotropic kainate/quisqualate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the putative metabotropic glutamate receptor antagonist 2-amino-3-phosphonopropionate (AP3) had no effect on the glutamate stimulated formation of inositol phosphates. We conclude that a metabotropic glutamate receptor is present on cochlear nucleus neurons of posthatch chicks and is able to stimulate formation of inositol phosphates.

2-Amino-5-phosphonovalerate↗