Hair cell regeneration in the avian cochlea: if it works in birds, why not in man?

Hearing loss caused by cochlear hair cell loss is the most common process afflicting the hearing impaired. Recent studies in the avian cochlea following ototoxic drug and noise damage have demonstrated a remarkable capacity for anatomical and functional recovery. Hair cell regeneration has been shown to play a major role in this recovery process.

Issues in neural plasticity as related to cochlear implants in children.

There is compelling evidence across species for a changing place code during development. This change in frequency organization may provide a mechanism for all elements within the central auditory pathways to receive the necessary stimulation to promote normal growth and development. We must take these normal developmental processes into consideration when deciding on the appropriate stimulation, training, and success procedures in cochlear implants in children.

Development of otoacoustic emissions in gerbil: evidence for micromechanical changes underlying development of the place code.

The development of the acoustic distortion product (ADP) 2f1-f2 was studied in gerbils, beginning 12 days after birth (P12). ADPs were measured as a function of stimulus frequency region (1.0 to 13.

Cochlear nucleus cell size is regulated by auditory nerve electrical activity.

Accumulating evidence suggests that sensorineural hearing loss in animals is rapidly followed by degenerative changes in central auditory neurons. For example, cochlear removal in birds and mammals results in a reduction in central auditory neuron cell size within 48 hours. A similar decrease in cell size after pharmacologic blockade of auditory nerve electrical activity with tetrodotoxin has been reported.

Hair cell regeneration in the avian inner ear.

The postembryonic production of hair cells in fish and reptiles has been known for several decades. Until recently it was assumed that this capacity was absent in the more highly specialized inner ears of birds and mammals. Recent research has shown, however, that birds have the capacity to rebuild a damaged inner ear.

Effects of cochlea removal on GABAergic terminals in nucleus magnocellularis of the chicken.

The effects of unilateral cochlea removal on GABA-immunoreactive (GABA-I) terminals in nucleus magnocellularis (NM) of the chick were assessed by immunocytochemical (ICC) techniques. Posthatch chicks (5-8 days old) survived from 1-37 days following unilateral cochlea removal. In the ipsilateral NM, the density of GABA-I terminals appeared to increase relative to normal controls 10-37 days after cochlea removal.

Effects of stimulus repetition rate on ABR threshold, amplitude and latency in neonatal and adult Mongolian gerbils.

The ABR wave forms of 16-day-old and adult Mongolian gerbils were evoked by click stimuli presented at rates ranging from 1 to 80/sec. Wave I and wave IV thresholds were determined for each of 5 click rates. Amplitudes and latencies of waves I and IV were measured at each of 7 click rates and 3 intensity levels (15, 40 and 65 dB above threshold).

Peripheral generators of the vestibular evoked potentials (VsEPs) in the chick.

Electrophysiological activity in response to linear acceleration stimuli was recorded from young chickens by means of subcutaneous electrodes. This investigation had 2 purposes: (1) to establish the vestibular origin of the potentials; and (2) to investigate the contribution of each vestibular labyrinth to the response. The stimuli consisted of pulses of linear acceleration delivered by a mechanical vibrator (shaker).

Ultrastructural observations on regenerating hair cells in the chick basilar papilla.

This experiment was designed to investigate cellular and subcellular maturational changes in regenerated immature sensory cells and support cells of the chick basilar papilla following gentamycin treatment. Scanning and transmission electron microscopy were used. The experimental animals received one subcutaneous injection of gentamycin sulfate daily (50 mg/kg) for five or 10 days.

Physiologic status of regenerated hair cells in the avian inner ear following aminoglycoside ototoxicity.

Regeneration of avian inner ear hair cells has been demonstrated after administration of aminoglycoside and after acoustic trauma. However, no published study to date has documented functional recovery of these regenerated sensory receptor cells. Newborn chicks were treated with gentamicin sulfate (50 mg/kg/day) for a total of either 5 (n = 10) or 10 (n = 76) days.

Reversible blockade of vestibular evoked activity in the chick.

Vestibular evoked potentials (VsEP) were recorded from young chickens following bilateral intralabyrinthine injections of Tetrodotoxin (TTX). The purpose of this study was to document the long term effects of TTX on the electrophysiological activity of the vestibular system. VsEP components were eliminated within 30 min of TTX injections.

Intermediate filaments in the inner ear of normal and experimentally damaged guinea pigs.

The hypothesis that proteins known to occur in glial cells in the central nervous system may be present in inner-ear supporting cells was investigated. Immunocytochemical techniques were used to look for the existence of two classes of intermediate filaments, vimentin and glial fibrillary acidic protein (GFAP), in cellular elements of the inner-ear epithelium in normal and experimentally damaged guinea-pig cochleas. Vimentin is present in two types of supporting cells in the normal organ of Corti: Deiters' cells and inner pillar cells.

Neuronal tracing with DiI: decalcification, cryosectioning, and photoconversion for light and electron microscopic analysis.

The molecule 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) is a fluorescent dye which diffuses within cell membranes. The properties of DiI diffusion and fluorescence are maintained in aldehyde-fixed tissue, thereby allowing selective neuronal tracing post mortem. We describe three modifications of this tracing method.

Afferent regulation of neurons in the brain stem auditory system.

We have reviewed a series of experiments which begin to examine the cellular events underlying afferent regulation of neuronal structure. Our initial interest in such experiments stemmed from a desire to understand the cellular nature of experiential influences on brain development. While this remains a long-range goal, it's elusive nature has become increasingly apparent; how will we know when such a goal is achieved? On the other hand, it has become increasingly clear that by approaching this question as a subset of the larger problem of tissue interactions regulating nervous system structure and function, some progress is possible.

Extracellular potassium influences DNA and protein syntheses and glial fibrillary acidic protein expression in cultured glial cells.

Previous reports of increases in glial cell number and expression of glial fibrillary acidic protein (GFAP) in stimulated brain regions or epileptic tissue have implicated a role for increases in extracellular potassium concentration ([K+]o) in glial reactions. We examined the effects of altered [K+]o on DNA and protein syntheses and GFAP expression of cultured glial cells isolated from the posthatch chick brain stem. [K+]o was varied by adding both KCl and NaCl to K+, NaCl-free medium to achieve final [K+] of 1-50 mM.

Cochlear ablation in deafness mutant mice: 2-deoxyglucose analysis suggests no spontaneous activity of cochlear origin.

Deafness mutant mice show no stimulus-related cochlear potentials as well as abnormal electrically-evoked responses recorded from the inferior colliculus. Abnormal spontaneous activity in the auditory periphery could result in abnormal development and/or maintenance of the central auditory pathways. We therefore assessed spontaneous activity of cochlear origin in the central nuclei of the mutants by ablating one cochlea and subsequently using the 2-deoxyglucose (2DG) technique to study metabolic activity.

[Vestibular evoked potentials in "Gallus Domesticus"].

Electrophysiological activity in response to linear acceleration stimuli was recorded from Gallus Domesticus by means of subcutaneous electrodes. This investigation had two purposes: 1) to obtain normative data for our laboratory, and 2) to rule out auditory and somatosensory contributions to the Vestibular Evoked Potentials (VsEP). The stimulus consisted of a sigmoid-shaped voltage function generated by a digital-to-analog converter.

Possible precursors of regenerated hair cells in the avian cochlea following acoustic trauma.

Hair cell regeneration following acoustic trauma to the avian cochlea has been documented using DNA labeling with tritiated thymidine. The goal of this study was to identify potential precursor cell populations for regenerating hair cells. Chicks were exposed in pairs to a 1500 Hz pure tone at 120 dBSPL for 18 h.

GABAergic neurons in brainstem auditory nuclei of the chick: distribution, morphology, and connectivity.

The second- and third-order auditory nuclei in the brainstem of the chicken, nucleus magnocellularis (NM) and nucleus laminaris (NL), receive afferents that are immunoreactive to gamma-aminobutyric acid (GABA). In order to investigate the source(s) of these GABAergic afferents, we examined the distribution, morphology, and connectivity of GABAergic neurons in and adjacent to NM and NL in chicks from 7 days of incubation to 12 days posthatch. Immunocytochemical techniques revealed the presence of approximately 150 GABA-labeled neurons within the neuropil surrounding NM and NL on each side of the brainstem.

Transient GABA immunoreactivity in cranial nerves of the chick embryo.

The distribution and time course of gamma-aminobutyric acid (GABA) immunoreactivity was investigated in the cranium of the chick embryo from 2 to 16 days of incubation (E2-16). A fraction of nerve fibers transiently stains GABA-positive in all cranial motor nerves and in the vestibular nerve. Cranial motor nerves stain GABA-positive from E4 to E11, including neuromuscular junctions at E8-11; labeled fibers are most frequent in the motor trigeminal root (E6-9.

Transneuronal regulation of protein synthesis in the brain-stem auditory system of the chick requires synaptic activation.

The cellular mechanisms by which afferents influence their target neurons were investigated using a slice preparation of the chick brain-stem auditory system. Each brain slice contained portions of the auditory nerve and the second-order auditory nucleus, nucleus magnocellularis (NM), bilaterally. NM neurons on one side of the slice were stimulated either orthodromically, via activation of the ipsilateral auditory nerve, or antidromically, via electrical stimulation of their axons.

Development of GABA immunoreactivity in brainstem auditory nuclei of the chick: ontogeny of gradients in terminal staining.

The development of gamma-aminobutyric acid-immunoreactivity (GABA-I) in nucleus magnocellularis (NM) and nucleus laminaris (NL) of the chick was studied by using an antiserum to GABA. In posthatch chicks, GABA-I is localized to small, round punctate structures in the neuropil and surrounding nerve cell bodies. Electron microscopic immunocytochemistry demonstrates that these puncta make synaptic contact with neuronal cell bodies in NM; thus, they are believed to be axon terminals.