Biomedical subjects

E W Rubel

Publications and source records attributed to E W Rubel.

At least 37 records · Page 2Linked to original sources

PubMed1999

The superior olivary nucleus and its influence on nucleus laminaris: a source of inhibitory feedback for coincidence detection in the avian auditory brainstem.

Located in the ventrolateral region of the avian brainstem, the superior olivary nucleus (SON) receives inputs from nucleus angularis (NA) and nucleus laminaris (NL) and projects back to NA, NL, and nucleus magnocellularis (NM). The reciprocal connections between the SON and NL are of particular interest because they constitute a feedback circuit for coincidence detection. In the present study, the chick SON was investigated. In vivo tracing studies show that the SON projects predominantly to the ipsilateral NM, NL, and NA. In vitro whole-cell recording reveals single-cell morphology, firing properties, and postsynaptic responses. SON neurons are morphologically and physiologically suited for temporal integration; their firing patterns do not reflect the temporal structure of their excitatory inputs. Of most interest, direct stimulation of the SON evokes long-lasting inhibition in NL neurons. The inhibition blocks both intrinsic spike generation and orthodromically evoked activity in NL neurons and can be eliminated by bicuculline methiodide, a potent antagonist for GABAA receptor-mediated neurotransmission. These results strongly suggest that the SON provides GABAergic inhibitory feedback to laminaris neurons. We discuss a mechanism whereby SON-evoked GABAergic inhibition can influence the coding of interaural time differences for sound localization in the avian auditory brainstem.

Animals↗

PubMed1999

High-frequency auditory feedback is not required for adult song maintenance in Bengalese finches.

Male Bengalese finches do not normally change their vocal patterns in adulthood; song is stereotyped and stable over time. Adult song maintenance requires auditory feedback. If adults are deafened, song will degrade within 1 week. We tested whether feedback of all sound frequencies is required for song maintenance. The avian basilar papilla is tonotopically organized; hair cells in the basal region encode high frequencies, and low frequencies are encoded in progressively apical regions. We restricted the spectral range of feedback available to a bird by killing either auditory hair cells encoding higher frequencies or those encoding both high and low frequencies and documented resultant changes in song. Birds were treated with either Amikacin alone to kill high-frequency hair cells or Amikacin and sound exposure to target hair cells across the entire papilla. During treatment, song was recorded from all birds weekly. After treatment and song recording, evoked-potential audiograms were evaluated on each bird, and papillas were evaluated by scanning electron microscopy. Results showed that hair cell damage over 46-63% of the basal papilla and the corresponding high-frequency hearing loss had no effect on song structure. In birds with hair cell damage extending further into the apical region of the papilla and corresponding low-frequency and high-frequency hearing loss, song degradation occurred within 1 week of beginning treatment and was comparable with degradation after surgical deafening. We conclude that either low-frequency spectral cues or temporal cues via feedback of the song amplitude envelope are sufficient for song maintenance in adult Bengalese finches.

Amikacin↗

PubMed1999

Life and death in otolaryngology: mechanisms of apoptosis and its role in the pathology and treatment of disease.

OBJECTIVES: To review recent advances in our understanding of programmed cell death, or apoptosis, and discuss implications of these basic science advances in our understanding of causes and potential treatments of a variety of diseases of the head and neck. DATA SOURCES: Basic science literature relevant to the study of apoptosis and its clinical implications. CONCLUSIONS: Apoptosis is now understood to be important in the normal development and survival of all multicellular organisms. Deregulation of this normally tightly controlled process underlies a variety of disease states, including neoplasia, autoimmune disease, and disorders of the central nervous system. A better understanding of this process and its regulation may help otolaryngologists better understand diseases relevant to this specialty and will lead to improved therapeutic interventions.

Apoptosis↗

PubMed1999

Recovery of the vestibulocolic reflex after aminoglycoside ototoxicity in domestic chickens.

Avian auditory and vestibular hair cells regenerate after damage by ototoxic drugs, but until recently there was little evidence that regenerated vestibular hair cells function normally. In an earlier study we showed that the vestibuloocular reflex (VOR) is eliminated with aminoglycoside antibiotic treatment and recovers as hair cells regenerate. The VOR, which stabilizes the eye in the head, is an open-loop system that is thought to depend largely on regularly firing afferents. Recovery of the VOR is highly correlated with the regeneration of type I hair cells. In contrast, the vestibulocolic reflex (VCR), which stabilizes the head in space, is a closed-loop, negative-feedback system that seems to depend more on irregularly firing afferent input and is thought to be subserved by different circuitry than the VOR. We examined whether this different reflex also of vestibular origin would show similar recovery after hair cell regeneration. Lesions of the vestibular hair cells of 10-day-old chicks were created by a 5-day course of streptomycin sulfate. One day after completion of streptomycin treatment there was no measurable VCR gain, and total hair cell density was approximately 35% of that in untreated, age-matched controls. At 2 wk postlesion there was significant recovery of the VCR; at this time two subjects showed VCR gains within the range of control chicks. At 3 wk postlesion all subjects showed VCR gains and phase shifts within the normal range. These data show that the VCR recovers before the VOR. Unlike VOR gain, recovering VCR gain correlates equally well with the density of regenerating type I and type II vestibular hair cells, except at high frequencies. Several factors other than hair cell regeneration, such as length of stereocilia, reafferentation of hair cells, and compensation involving central neural pathways, may be involved in behavioral recovery. Our data suggest that one or more of these factors differentially affect the recovery of these two vestibular reflexes.

Aminoglycosides↗

PubMed1999

Glutamate regulates IP3-type and CICR stores in the avian cochlear nucleus.

Neurons of the avian cochlear nucleus, nucleus magnocellularis (NM), are activated by glutamate released from auditory nerve terminals. If this stimulation is removed, the intracellular calcium ion concentration ([Ca2+]i) of NM neurons rises and rapid atrophic changes ensue. We have been investigating mechanisms that regulate [Ca2+]i in these neurons based on the hypothesis that loss of Ca2+ homeostasis causes the cascade of cellular changes that results in neuronal atrophy and death. In the present study, video-enhanced fluorometry was used to monitor changes in [Ca2+]i stimulated by agents that mobilize Ca2+ from intracellular stores and to study the modulation of these responses by glutamate. Homobromoibotenic acid (HBI) was used to stimulate inositol trisphosphate (IP3)-sensitive stores, and caffeine was used to mobilize Ca2+ from Ca2+-induced Ca2+ release (CICR) stores. We provide data indicating that Ca2+ responses attributable to IP3- and CICR-sensitive stores are inhibited by glutamate, acting via a metabotropic glutamate receptor (mGluR). We also show that activation of C-kinase by a phorbol ester will reduce HBI-stimulated calcium responses. Although the protein kinase A accumulator, Sp-cAMPs, did not have an effect on HBI-induced responses. CICR-stimulated responses were not consistently attenuated by either the phorbol ester or the Sp-cAMPs. We have previously shown that glutamate attenuates voltage-dependent changes in [Ca2+]i. Coupled with the present findings, this suggests that in these neurons mGluRs serve to limit fluctuations in intracellular Ca2+ rather than increase [Ca2+]i. This system may play a role in protecting highly active neurons from calcium toxicity resulting in apoptosis.

Adenylyl Cyclase Inhibitors↗

PubMed1999

Delta1 expression during avian hair cell regeneration.

Postembryonic production of hair cells, the highly specialized receptors for hearing, balance and motion detection, occurs in a precisely controlled manner in select species, including avians. Notch1, Delta1 and Serrate1 mediate cell specification in several tissues and species. We examined expression of the chicken homologs of these genes in the normal and drug-damaged chick inner ear to determine if signaling through this pathway changes during hair cell regeneration. In untreated post-hatch chicks, Delta1 mRNA is abundant in a subpopulation of cells in the utricle, which undergoes continual postembryonic hair cell production, but it is absent from all cells in the basilar papilla, which is mitotically quiescent. By 3 days after drug-induced hair cell injury, Delta1 expression is highly upregulated in areas of cell proliferation in both the utricle and basilar papilla. Delta1 mRNA levels are elevated in progenitor cells during DNA synthesis and/or gap 2 phases of the cell cycle and expression is maintained in both daughter cells immediately after mitosis. Delta1 expression remains upregulated in cells that differentiate into hair cells and is downregulated in cells that do not acquire the hair cell fate. Delta1 mRNA levels return to normal by 10 days after hair cell injury. Serrate1 is expressed in both hair cells and support cells in the utricle and basilar papilla, and its expression does not change during the course of drug-induced hair cell regeneration. In contrast, Notch1 expression, which is limited to support cells in the quiescent epithelium, is increased in post-M-phase cell pairs during hair cell regeneration. This study provides initial evidence that Delta-Notch signaling may be involved in maintaining the correct cell types and patterns during postembryonic replacement of sensory epithelial cells in the chick inner ear.

Animals↗

PubMed1998

Glutamatergic and GABAergic agonists increase [Ca2+]i in avian cochlear nucleus neurons.

Neurons of the avian cochlear nucleus, nucleus magnocellularis (NM), are stimulated by glutamate, released from the auditory nerve, and GABA, released from both interneurons surrounding NM and from cells located in the superior olivary nucleus. In this study, the Ca2+ indicator dye Fura-2 was used to measure Ca2+ responses in NM stimulated by glutamate- and GABA-receptor agonists using a chicken brainstem slice preparation. Glutamatergically stimulated Ca2+ responses were evoked by kainic acid (KA), alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA), and N-methyl-D-aspartate (NMDA). KA- and AMPA-stimulated changes in [Ca2+]i were also produced in NM neurons stimulated in the presence of nifedipine, an L-type Ca2+ channel blocker, suggesting that KA- and AMPA-stimulated changes in [Ca2+]i were carried by Ca2(+)-permeable receptor channels. Significantly smaller changes in [Ca2+]i were produced by NMDA. When neurons were stimulated in an alkaline (pH 7.8) superfusate, NMDA responses were potentiated. KA- and AMPA-stimulated responses were not affected by pH. Several agents known to stimulate metabotropic receptors in other systems were tested on NM neurons bathed in a Ca2+ free-EGTA--buffered media, including L-cysteine sulfinic acid (L-CSA), trans-azetidine dicarboxylic acid (t-ADA), trans-aminocyclo-pentanedicarboxylic acid (t-ACPD), and homobromoibotenic acid (HBI). The only agent to reliably and dose-dependently increase [Ca2+]i was HBI, an analog of ibotenate. GABA also stimulated increases in [Ca2+]i in NM neurons. GABA-stimulated responses were reduced by agents that block voltage-operated channels and by agents that inhibit Ca2+ release from intracellular stores. Whereas GABA-A receptor agonist produced increases in [Ca2+]i GABA-B and GABA-C receptor agonists had no effect. There appear to be several ways for [Ca2+]i to increase in NM neurons. Presumably, each route represents a means by which Ca2+ can alter cellular processes.

Animals↗

PubMed1998

Development of single- and two-tone responses of anteroventral cochlear nucleus neurons in gerbil.

Responses of anteroventral cochlear nucleus (AVCN) neurons in developing gerbils were obtained to single-tone stimuli, and two-tone stimuli elicited by best frequency probes presented over a range of intensities. Neurons displayed Type I, Type I/III, and Type III receptive field patterns. Best frequencies ranged from 1.5 to 10.0 kHz. Two-tone suppression (2TS) was first observed in 5 of 16 neurons examined at 14 dab. and in all neurons examined in gerbils aged 15 to 60 dab. Suppression areas grew larger, and discharge rate reductions became greater with age. Features of the two-tone responses that were highly correlated with single-tone responses across age groups include maximum rate reductions and suppression area thresholds. The intensity level of the CF probe-tone also influenced these features of 2TS. Maximum rate reductions to below spontaneous rate levels of activity were common across age groups. Results suggest that the cochlear amplifier is present and fundamentally adult-like by 15 dab for the regions of the cochlea coding the mid frequencies in gerbil. Over the subsequent week, contributions to the developing two-tone responses by the cochlear amplifier increase slightly. Two-tone responses are influenced by central inhibitory mechanisms as early as 14 dab.

Acoustic Stimulation↗

PubMed1998

Development of the base of the cochlea: place code shift in the gerbil.

Distortion product otoacoustic emission measurements were made at 1/12 octave intervals before and after the injection of furosemide in gerbils aged 15 days after birth to adult, in order to obtain estimates of cochlear amplifier gain as a function of stimulus frequency. The frequency at which the gains went sharply to zero, defined as the 'base cutoff frequency', increased from about 20 kHz to over 50 kHz during development. This increase provides further confirmation of the hypothesis that the place code changes during development in the basal part of the cochlea. If the measured base cutoff frequency is identified with the characteristic frequency at the basal end of the cochlea, as defined by electrophysiological measures, then these emission data can be used to generate a frequency-place map as a function of age. The derived place code shift is consistent with published electrophysiological measures, and can be used to extend these measures. Near the base cutoff frequency, the observed cochlear amplifier gain typically dropped sharply from a relative maximum to zero, over a distance of about a half octave. Specifically, this distance appeared to exhibit a curvilinear variation with age, reaching a maximum of 3/4 of an octave at 19-21 days. After transforming from frequency to place using the map derived from emissions, however, the distance between the extreme base and the place associated with the peak gain decreased monotonically from about 1.2 mm at age 15-19 days to 0.6 mm at maturity. This distance is assumed to be characteristic of the length of the active amplification zone for the cochlear amplifier in the base region. Over the same time period, there was approximately a doubling of the rate of amplification with distance from the base, so that the cochlear amplifier gain at the peak actually changed very little from 15 days to adult.

Acoustic Stimulation↗

PubMed1998

Expression of novel potassium channels in the chick basilar papilla.

Ionic currents are critical for the functioning of the inner ear auditory sensory epithelium. We set out to identify and molecularly clone the genes encoding the channels responsible for several currents in the chick basilar papilla. Here we describe an inward-rectifying K+ channel, cKir2.3, present in both hair cells and support cells in the apical end of the chick basilar papilla. The biophysical properties of the human ortholog, hKir2.3, are similar to those of an inward-rectifying channel found in the apical end of the chick basilar papilla, suggesting that this channel may contribute to the corresponding current. Additionally, we describe two new members of the Kv6 subfamily of putative regulatory voltage-gated K channels, cKv6.2 and cKv6.3. Both are expressed in hair cells in the apical end of the chick basilar papilla; cKv6.2 is also strongly expressed in support cells and in the brain.

Amino Acid Sequence↗

PubMed1998

Recent insights into regeneration of auditory and vestibular hair cells.

Advances in hair cell regeneration are progressing at a rapid rate. This review will highlight and critique recent attempts to understand some of the cellular and molecular mechanisms underlying hair cell regeneration in non-mammalian vertebrates and efforts to induce regeneration in the mammalian inner ear sensory epithelium.

Animals↗

PubMed1998

Auditory perception following hair cell regeneration in European starling (Sturnus vulgaris): frequency and temporal resolution.

Behavioral detection thresholds, auditory filter widths, and temporal modulation transfer functions were obtained from four starlings before, during and after 11 days of subcutaneous injections of kanamycin, an aminoglycoside antibiotic. Birds were operantly conditioned to respond to pure tones and amplitude modulated noises ranging in frequency from 0.25 to 7 kHz using adaptive staircase procedures and were tested daily for 92 days after the first injection of aminoglycoside. All birds had threshold shifts of at least -60 dB at frequencies above 4 kHz. Lower frequencies were affected in some birds, although none of the birds had hearing loss below 3 kHz. All four birds had wider auditory filters at 5 kHz immediately after the aminoglycoside series. Any changes in frequency resolution at frequencies below 5 kHz were slight, transitory, and rarely observed. Two of the four birds had permanently wider auditory filters at 5 kHz. Temporal modulation transfer functions were briefly affected in two birds during the time of greatest threshold shift. Recovery of detection thresholds began soon after the injections ceased and continued for approximately 60 days. Recovery in frequency resolution lagged behind auditory threshold by about 10 days. Normal temporal resolution was observed in the context of impaired intensity and frequency resolution. Changes in auditory threshold and frequency resolution were closely associated for all birds at 5 kHz, but were correlated with statistical significance in only two birds. Scanning electron microscopy was performed on all four birds after 90 days of recovery and confirmed that the extent of initial damage was consistent with the pattern of observed hearing loss.

Animals↗

PubMed1998

Activity-dependent regulation of [Ca2+]i in avian cochlear nucleus neurons: roles of protein kinases A and C and relation to cell death.

Neurons of the cochlear nucleus, nucleus magnocellularis (NM), of young chicks require excitatory afferent input from the eighth nerve for maintenance and survival. One of the earliest changes seen in NM neurons after deafferentation is an increase in intracellular calcium concentration ([Ca2+]i). This increase in [Ca2+]i is due to loss of activation of metabotropic glutamate receptors (mGluR) that activate second-messenger cascades involved in [Ca2+]i regulation. Because mGluRs are known to act via the phospholipase C and adenylate cyclase signal transduction pathways, the goal of this study was to determine the roles of protein kinases A (PKA) and C (PKC) activities in the regulation of NM neuron [Ca2+]i by eighth nerve stimulation. Additionally, we sought to determine the relationship between increased [Ca2+]i and cell death as measured by propidium iodide incorporation. [Ca2+]i of individual NM neurons in brain stem slices was monitored using fura-2 ratiometric fluorescence imaging. NM field potentials were monitored in experiments in which the eighth nerve was stimulated. Five hertz orthodromic stimulation maintained NM neuron [Ca2+]i at approximately 110 nM for 180 min. In the absence of stimulation, NM neuron [Ca2+]i increased steadily to a mean of 265 nM by 120 min. This increase was attenuated by superfusion of PKC activators phorbol-12,13-myristate acetate (100 nM) or dioctanoylglycerol (50 microM) and by activators of PKA: 1 mM 8-bromoadenosine-3',5'-cyclophosphate sodium (8-Br-cAMP), 50 microM forskolin or 100 microM Sp-adenosine 3',5'-cyclic monophosphothioate triethylamine. Inhibition of PKA (100 microM Rp-cAMPS) or PKC (50 nM bisindolymaleimide or 10 microM U73122) during continuous orthodromic stimulation resulted in an increase in NM neuron [Ca2+]i that exceeded 170 and 180 nM, respectively, by 120 min. Nonspecific kinase inhibition with 1 microM staurosporine during stimulation resulted in an [Ca2+]i increase that was greater in magnitude than that seen with either PKA or PKC inhibition alone, equal to that seen in the absence of stimulation, but much smaller than that seen with inhibition of mGluRs. In addition, manipulations that resulted in a [Ca2+]i increase >/=250 nM resulted in an increase in number and percentage of propidium iodide-labeled NM neurons. These results suggest that eighth nerve activity maintains [Ca2+]i of NM neurons at physiological levels in part via mGluR-mediated activation of PKA and PKC and that increases in [Ca2+]i due to activity deprivation or interruption of the PKA and PKC [Ca2+]i regulatory mechanisms are predictive of subsequent cell death.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1997

Rapid regulation of cytoskeletal proteins and their mRNAs following afferent deprivation in the avian cochlear nucleus.

During development, removal of neuronal input can lead to profound changes in postsynaptic cells, including atrophy and cell death. In the chicken brainstem cochlear nucleus, the nucleus magnocellularis (NM), deprivation of auditory input via unilateral cochlea removal or silencing the eighth nerve with tetrodotoxin leads to a loss of 25-30% of the neurons and the atrophy of surviving neurons. One intracellular component that may be involved in both cell atrophy and cell death is the cytoskeleton. The degradation of the cytoskeleton following deafferentation could potentially lead to either atrophy or death of NM neurons. However, little is known regarding the role of neuronal input on the cytoskeletal structure of NM neurons and whether changes in the cytoskeleton are responsible for cell death following deafferentation. The present study examined whether changes in the cytoskeleton of NM neurons occurred following cochlea removal. Several components of the cytoskeleton were analyzed following unilateral afferent deprivation. Levels of immunostaining for tubulin, actin, and microtubule-associated protein 2 (MAP-2), and levels of beta-tubulin and beta-actin mRNAs were assessed in NM neurons following cochlea removal. Our results revealed that afferent deprivation results in a rapid decrease in immunostaining for all three cytoskeletal proteins examined. These decreases were observed as early as 3 hours after cochlea removal and persisted for up to 4 days. In addition, these changes occurred in all deafferented NM neurons at the early time points, indicating that both dying and surviving NM neurons undergo a similar change in their cytoskeletons. In contrast to the decreases in immunostaining, levels of beta-tubulin and beta-actin mRNAs were not noticeably altered by deafferentation. Our findings indicate that the cytoskeleton is altered or degraded following deafferentation but that this process is not regulated at the transcriptional level.

Afferent Pathways↗

PubMed1997

Bengalese finches Lonchura Striata domestica depend upon auditory feedback for the maintenance of adult song.

Male birds of age-limited song-learning species develop their full song repertoires in the first year of life. For this type of song learner, once song is stabilized in adulthood, it is highly stereotyped and stable over time. Traditionally, it has been believed that age-limited song learners do not depend on auditory feedback for the maintenance of adult song. A recent report, however, showed that adult song in zebra finches, age-limited learners, does change after long-term deafness. We report here that another species of age-limited learner, Bengalese finches, depends critically on auditory feedback for adult song maintenance. We surgically deafened adult males and recorded song for 12 weeks after surgery. Results show that song degraded significantly within 1 week of surgery and continued to degrade over the next 11 weeks. This represents a more rapid degradation of song than has been seen previously in age-limited species. Song deficits after deafening included a marked decrease in syllable sequence stereotypy, skewed syllable distribution within song bouts, degradation of syllable phonology, and dropped, combined, and new or unrecognizable syllables. Decreased sequence stereotypy and combined syllables appeared within 1 week of deafening and did not worsen over time. Skewed syllable distributions and syllable phonology changes appeared after 1 week and did worsen. Occurrences of dropped and new syllables appeared within 1 week and increased over time. Comparison with other species indicates that much variability exists among species in the extent to which auditory feedback is necessary for song maintenance.

Acoustic Stimulation↗

PubMed1997

Development of Cat-301 immunoreactivity in auditory brainstem nuclei of the gerbil.

The developing brainstem auditory system has been studied in detail by using anatomical and physiological techniques. However, it is not known whether immature auditory neurons exhibit different molecular characteristics than those of physiologically mature neurons. To address this issue, we examined the distribution of Cat-301 immunoreactivity in the developing auditory brainstem of gerbils. Cat-301 is a monoclonal antibody that recognizes a 680-kD chondroitin sulfate proteoglycan similar to aggrecan, a high-molecular-weight chondroitin sulfate proteoglycan found in cartilage. In the central nervous system, Cat-301 immunoreactivity is localized to the extrasynaptic surface of neurons. It has been hypothesized by Hockfield and co-workers (Hockfield et al. [1990a]Cold Spring Harbor Symp. Quart. Biol. 55:504-514) that the Cat-301 proteoglycan is a molecular marker indicating that a neuron has acquired mature neuronal properties. In the current study, Cat-301 staining is first seen at 7 days after birth in the anterior ventral cochlear nucleus (AVCN), the posterior VCN (PVCN), and the medial nucleus of the trapezoid body (MNTB) shortly before the onset of sound-evoked activity. By 21 days after birth, neurons in the AVCN, the PVCN, and the lateral and medial superior olive have attained adult-like distributions of Cat-301 staining concomitant with the physiological maturation of these neurons. Neurons in MNTB attain adult-like distributions of Cat-301 immunoreactivity at 1 year. The maturation of Cat-301 immunoreactivity parallels the physiological maturation of gerbil auditory neurons, and the Cat-301 proteoglycan may play a role in the formation and/or stabilization of auditory synapses.

Animals↗

PubMed1997

Induction of cell proliferation in avian inner ear sensory epithelia by insulin-like growth factor-I and insulin.

Postembryonic production of inner-ear hair cells occurs both normally and after insult in lower vertebrates and avians. To determine how this proliferation is controlled, several growth factors were tested for effects on progenitor-cell division in cultured avian vestibular sensory epithelium. Mitogenic effects of bombesin, epidermal growth factor, insulin-like growth factor-I (IGF-I), insulin, and transforming growth factor-alpha were assayed in organo-typic cultures of utricles from the mature, undamaged (normal) chicken inner ear. Tritiated thymidine and autoradiographic techniques and 5-bromo-2'-deoxyuridine (BrdU) immunocytochemistry were used to identify cells synthesizing DNA. IGF-I stimulated DNA synthesis in the vestibular sensory receptor epithelium in a dose-dependent manner. DNA synthesis was also stimulated by insulin. These results suggest that stimulation of the IGF-I receptors by IGF-I or insulin binding stimulates cell proliferation in the mature avian vestibular sensory epithelium.

Animals↗

PubMed1997

Neurofilament proteins in avian auditory hair cells.

The distribution of middle-weight neurofilament protein (NF-M), an intermediate filament of neurons, was examined in the developing and mature avian inner ear by using immunocytochemical techniques. NF-M was detected in auditory hair cells and VIIIth cranial nerve neurons. NF-M-positive hair cells are first detected at embryonic day 11 (E11) in superior hair cells in the mid-proximal (mid-frequency) region of the chicken basilar papilla. With time, increasing numbers of hair cells express NF-M. Two developmental gradients occur: 1) a radial gradient, in which superior hair cells are labeled first, and progressively more inferiorly located hair cells are labeled during ontogeny, and 2) a longitudinal gradient, in which hair cells in the mid-proximal region are labeled first, and then progressively more distal (low-frequency) hair cells are labeled. There is also a small proximally directed progression of NF-M expression. By E19, NF-M-positive hair cells are found throughout the distal and mid-proximal regions, and this expression is maintained through 3 weeks posthatching. By 22 weeks posthatching, NF-M staining in hair cells is markedly diminished; staining is seen in only a few tall hair cells in the distal one-fourth of the papilla and in short hair cells in the distal one-half of the papilla. NF-M is never expressed by hair cells at the proximal (high-frequency) end of the papilla at any time examined. These findings suggest that some cell types that have traditionally been classified as nonneural may express neurofilament and that the basilar papilla of the neonatal chicken is not morphologically mature.

Animals↗