[Show abstract][Hide abstract] ABSTRACT: Immunostaining mouse cochleas for tyrosine hydroxylase (TH) and dopamine beta-hydroxylase suggests that there is a rich adrenergic innervation throughout the auditory nerve trunk and a small dopaminergic innervation of the sensory cell areas. Surgical cuts in the brainstem confirm these dopaminergic fibers as part of the olivocochlear efferent bundle. Within the sensory epithelium, TH-positive terminals are seen only in the inner hair cell area, where they intermingle with other olivocochlear terminals expressing cholinergic markers (vesicular acetylcholine transporter; VAT). Double immunostaining suggests little colocalization of TH and VAT; quantification of terminal volumes suggests that TH-positive fibers constitute only 10-20% of the efferent innervation of the inner hair cell area. Immunostaining of mouse brainstem revealed a small population of TH-positive cells in and around the lateral superior olive. Consistent with cochlear projections, double staining for the cholinergic marker acetylcholinesterase suggested that TH-positive somata are not cholinergic and vice versa. All observations are consistent with the view that a small dopaminergic subgroup of lateral olivocochlear neurons 1) projects to the inner hair cell area, 2) is distinct from the larger cholinergic group projecting there, and 3) may correspond to lateral olivocochlear "shell" neurons described by others (Warr et al.  Hear. Res 108:89-111).
The Journal of Comparative Neurology 09/2006; 498(3):403-14. DOI:10.1002/cne.21050 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been hypothesized that normal pruning of exuberant branching of afferent neurons in the developing cochlea is caused by the arrival of the olivocochlear efferent neurons and the resulting competition for synaptic sites on hair cells. This hypothesis was supported by a report that afferent innervation density on mature outer hair cells (OHCs) is elevated in animals deefferented at birth, before the olivocochlear system reaches the outer hair cell area (Pujol and Carlier  Dev. Brain Res. 3:151-154). In the current study, this claim was evaluated quantitatively at the electron microscopic level in four cats that were de-efferented at birth and allowed to survive for 6-11 months. A semiserial section analysis of 156 OHCs from de-efferented and normal ears showed that, although de-efferentation essentially was complete in all four cases, the number and distribution of afferent terminals on OHCs was indistinguishable from normal, and the morphology of afferent synapses was normal in both the inner hair cell area and the OHC area. Thus, the postnatal presence of an efferent system is not required for the normal development of cochlear afferent innervation, and the synaptic competition hypothesis is not supported.
The Journal of Comparative Neurology 08/2000; 423(1):132-9. DOI:10.1002/1096-9861(20000717)423:13.0.CO;2-7 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper describes some central terminations of type II spiral ganglion neurons as labeled by extracellular injections of horseradish peroxidase (HRP) into the auditory nerve of cats. After histological processing with diaminobenzidine, both thick (2-4 microns) and thin (0.5 microns) fibers of the auditory nerve were stained. Whenever traced, thick fibers always originated from type I spiral ganglion neurons and thin fibers always from type II ganglion neurons. Because the labeling of type II axons faded as fibers projected into the cochlear nucleus, this report is limited to regions of the ventral cochlear nucleus near the auditory nerve root. The central axons of type II neurons are unmyelinated, have simple yet variable branching patterns in the cochlear nucleus, and form both en passant and terminal swellings. Under the light microscope, most swellings are located in the neuropil but they are also found in the vicinity of cell bodies, nodes of Ranvier of type I axons, and blood vessels. Eighteen en passant swellings in the neuropil were located by light microscopy and resectioned for electron microscopy; two of these swellings exhibited ultrastructural features characteristic of chemical synapses. The data indicate that inputs from outer hair cells might be able to influence auditory processing in the cochlear nucleus through type II primary neurons.
The Journal of Comparative Neurology 06/1991; 308(2):209-23. DOI:10.1002/cne.903080208 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study was to describe the longitudinal and radial gradients of cochlear innervation in the cat. To this end, afferent and efferent terminals of both the inner (IHC) and outer hair cell (OHC) regions were reconstructed from serial ultrathin sections at six and eight cochlear locations, respectively, corresponding to roughly octave intervals of characteristic frequency (CF). Analysis of the afferent innervation of the IHCs showed 1) the number of radial fibers per IHC rises from 10 per IHC at the 0.25 kHz region to a maximum of 30 per IHC at the 10 kHz locus; 2) branching of radial fibers is essentially restricted to regions apical to the 1.0 kHz point; and 3) there are significant differences in synaptic-body morphology for synapses on different sides of the IHC, corresponding to known differences in afferent threshold and rate of spontaneous activity. With respect to efferent innervation in the IHC area, we found 1) that there were numerous vesicle-filled terminals contacting every IHC examined; however, those with obvious synaptic specialization were confined to the most apical regions; and 2) there were roughly the same numbers of efferent synapses per radial fiber at all cochlear locations; however, at each location, radial fibers contacting the modiolar side of the hair cell (corresponding to high-threshold afferents) showed significantly more efferent synapses than radial fibers contacting the pillar side. Analysis of the OHC afferent innervation showed 1) a clear rise in numbers of terminals per OHC from roughly 3 per cell in the base to 15 per cell in the apex, 2) no systematic differences in the numbers of terminals as a function of OHC row, and 3) that synaptic bodies at the OHC afferent synapse are common only apical to the 1.0 kHz locus. Counts of efferent terminals on OHCs revealed 1) maximal numbers (9 per OHC) between the 6 and 24 kHz regions and 2) striking decrease in terminal counts from first- to third-row OHCs. Ultrastructural data on efferent innervation were compared quantitatively with light-microscopic analysis of cochleas immunostained (with antibody to synaptophysin) to reveal all vesiculated terminals.
The Journal of Comparative Neurology 11/1990; 301(3):443-60. DOI:10.1002/cne.903010309 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Single-unit recordings were made from populations of auditory-nerve fibers in 12 cats before and after acoustic overstimulation. Cats were killed 4 to 16 h after exposure, and the cochleas were analyzed at the light- and electron-microscopic levels. The exposures were designed to create 40 to 60 dB of acute threshold shift. Physiological changes were similar to those seen in cases of permanent threshold shift: tuning curves with elevation of 'tips' and 'tails' were associated with significant decreases in the mean spontaneous discharge rates; tuning curves with elevated tips but hypersensitive tails were associated with clear elevation of the mean spontaneous rates. At the light-microscopic level, none of the ears showed any significant stereociliary pathology. Some of the ears showed no light-microscopic pathology whatsoever, while others showed signs of swelling and vacuolization in both inner and outer hair cell areas in cochlear regions appropriate to the CF regions showing threshold shifts. The presence or absence of these light-microscopic changes was, to some extent, dependent on the nature of the exposure stimulus. At the electron-microscopic level, in addition to apparent swelling of radial afferent terminals, the inner hair cells themselves were swollen. In two cochlear regions (from two ears) which showed acute threshold shifts of 20 to 40 dB, but no light-microscopic changes, serial-section ultrastructural analysis of stereocilia and cuticular plates was performed. In contrast to the situation in ears with permanent threshold shifts [(1986) Hear Res. 26, 65-88], there was no pathology in the intracuticular portion of the stereocilia rootlets. There were, however, significant changes in the lengths of the supracuticular portion of the rootlets. It is suggested that this attenuation of the supracuticular rootlet could decrease the stiffness of the stereocilia tufts and thereby change the tuning properties and sensitivity of the cochlear partition.
Hearing Research 02/1987; 26(1):45-64. DOI:10.1016/0378-5955(87)90035-9 · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Of the roughly 50,000 afferent fibers in the cat’s auditory nerve, approximately 95% terminate peripherally on inner hair cells (IHCs), as the so-called “radial fibers” (RFs) [24,25]. RFs comprise the population of neurons sampled when the auditory nerve is impaled with glass microelectrodes . In the cat, the great majority of RFs is unbranched, terminating on a single IHC via a single terminal swelling [24,8]. Thus, by sampling the activity of a single RF we have a window onto the functional state of a very restricted region of the organ of Corti. By sampling the activity of different single fibers, with different characteristic frequencies (CFs), we can assess the functional state of the entire cochlea, from base to apex.
Basic and Applied Aspects of Noise-Induced Hearing Loss, 01/1986: pages 163-177; , ISBN: 978-1-4684-5178-8
[Show abstract][Hide abstract] ABSTRACT: Tuning curves were obtained from 100 to 150 auditory-nerve fibers spanning the range of characteristic frequencies (CFs) in each of eight cases of permanent noise-induced and three cases of permanent kanamycin-induced threshold shift. In each ear, from one to six neurons were intracellularly labeled with horseradish peroxidase. Locating the labeled terminals in plastic-embedded surface preparations of the cochlea enabled us to accurately correlate particular tuning-curve abnormalities with the condition of the sensory cells generating them. The correlations between structural and functional changes suggest that a normal tuning-curve tip requires that the stereocilia on both the IHCs and OHCs (especially those from the first row) be normal. Selective damage to the OHCs is associated with elevation of the tips and hypersensitivity of the tuning-curve tails. This tuning-curve pattern also originates from cochlear regions at the basal border of hair cell lesions where the local hair cells (and their stereocilia) appear completely normal at the light-microscopic level. Total destruction of the OHCs in a region in which the IHCs appear normal (as can happen in cases of kanamycin poisoning) is associated with bowl-shaped tuning curves which appear to lack a tip. Combined damage to the IHCs and OHCs (as typically happens in cases of acoustic trauma) is invariably associated with elevation of both tips and tails on the tuning curve. A framework for the interpretation of the results is suggested in which the activity of the OHCs is transmitted via the tectorial membrane to the tall row of stereocilia on the IHCs.
Hearing Research 11/1984; 16(1):55-74. DOI:10.1016/0378-5955(84)90025-X · 2.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The spontaneous discharge rates (SRs) sampled from auditory-nerve fibers in cases of chronic cochlear pathology are often abnormally low . The application of intracellular labeling techniques to noise-exposed ears makes it possible to accurately correlate fiber populations showing SR abnormalities with the cochlear locations from which these responses originate. The correlations reveal that a decrease in the mean rates of spontaneous discharge is typically associated with selective loss of the tallest row of stereocilia from the inner hair cells. In cochlear regions where virtually all of the tall stereocilia are missing from the inner hair cells, the maximum rates of spontaneous discharge are less than 1/3 normal values. We suggest that the loss of tall stereocilia causes the decrease in SR because much of the resting current in the inner hair cell normally flows through the stereocilia membrane. Thus, the loss of that membrane leads to a hyperpolarization of the inner hair cell which, in turn, decreases the spontaneous release of vesicles at the synapse. An interpretation is also suggested for the "compression" of the SR distribution commonly seen among high-frequency neurons in normal animals .
Hearing Research 11/1984; 16(1):43-53. DOI:10.1016/0378-5955(84)90024-8 · 2.97 Impact Factor