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N K Woolf

Publications and source records attributed to N K Woolf.

At least 37 records · Page 2Linked to original sources

Ontogeny of neural discharge patterns in the ventral cochlear nucleus of the mongolian gerbil.

Discharge patterns were recorded extracellularly from single neurons in the ventral cochlear nucleus (VCN) of Mongolian gerbils ranging in age from 10 days after birth (DAB) to adult, a period which includes the onset of responsiveness to acoustic stimulation. At 10 DAB none of the neurons encountered within the VCN responded to acoustic stimulation. At 12 DAB approximately 15% of the neurons isolated in VCN were responsive. This coincided with the earliest cochlear microphonic potentials and preceded the appearance of the cochlear compound action potential (AP) by two days. At 14 DAB, or older, the great majority of neurons isolated in VCN responded to acoustic stimulation. Most parameters of VCN neural function exhibited significant changes between 12 and 18 DAB: neural thresholds improved approximately 100 dB; mean spontaneous discharge rate increased; the high-frequency range of characteristic frequency (CF) values increased from 10.0 to 24.0 kHz; the upper limit for phase locking increased from 0.8 kHz to 3.0 kHz; dynamic range increased from 16 dB to 44 dB, and the proportion of units with well-defined initial onset peaks in their post-stimulus-time (PST) response patterns increased from 40% to 100% of units. Most of the neural parameters examined achieved adult characteristics by 18 DAB. Frequency tuning (Q10dB) matured earlier for high-CF units. The most sharply tuned neurons with high CFs (greater than 4 kHz) at 12 DAB had Q10dB values equal to those for adults. None of the neurons with low CFs (less than 4 kHz) had Q10dB values greater than 1.2 at this age. Classical 'on' PST response patterns were not seen at 12 and 14 DAB. A unique PST response type, characterized by very long latency phasic discharge, was observed only at 12 DAB. None of the VCN neurons recorded from 12 DAB subjects displayed rhythmic 'bursting' or 'pulsing' PST response patterns, as has been reported at the earliest stages of functional development in the VCN of the cat. Most units were capable of sustained discharge, even with long stimulus durations. Units with 'primary-like' PST response patterns at 12 exhibited greater variability in first spike latency and less pronounced initial rates of firing than was characteristic in adults, resulting in poorly defined onset peaks. In contrast, units with chopper PST response patterns showed well-defined onset peaks.

Animals↗

Cochlear deoxyglucose uptake: relationship to stimulus intensity.

The relationship between stimulus intensity and the uptake of 2-deoxyglucose (2-DG) in the cochlea of the gerbil was studied using an autoradiographic technique. In silence, incorporation of labeled 2-DG into stria vascularis and the spiral ligament was significantly higher than for other inner ear structures. With increasing intensity of noise exposure, 2-DG uptake in the spiral ganglion and VIIIth nerve increased dramatically when compared to the lateral wall structures. In contrast, relative 2-DG uptake in the organ of Corti was much less affected by noise exposure. Only at 105 dB SPL, the highest intensity tested, was a modest but statistically significant increase observed in the sensory epithelium. The small change in relative 2-DG uptake observed in the organ of Corti during acoustic stimulation is consistent with Davis' (1965: Quant. Biol. 30, 181-190) battery model of the cochlear transduction process. Alternatively, a larger change may have occurred, but been restricted to a small portion of the epithelium, such as one or both populations of hair cells.

Acoustic Stimulation↗

The development of auditory function in the cochlea of the mongolian gerbil.

Cochlear microphonic (CM) potentials were recorded throughout the development of auditory function in the Mongolian gerbil. CM responses were first recorded at 12 days after birth (DAB), with thresholds exceeding 103 dB SPL. CM thresholds subsequently improved rapidly in a parallel fashion across the responsive frequency range, achieving adult levels by 18 DAB. There was no evidence from CM thresholds of a preferential rate of maturation for either the high or low frequency ranges. CM responses to suptrathreshold stimulation were also studied throughout development. At all responsive ages, CM input-output functions increased logarithmically to a saturating maximum value and then declined. Maximum CM responses increased continuously throughout development in a parallel fashion across all frequencies. The dynamic range of the CM input-output functions (the intensity interval from CM threshold to maximum CM value) also developed in a parallel manner across frequencies, but reached mature assymptotic values by 16 DAB. The results suggest that throughout the adult CM frequency range cochlear hair cell function develops simultaneously.

Age Factors↗

Immunologic and electrophysiological response to cytomegaloviral inner ear infection in the guinea pig.

We investigated the development of labyrinthitis in animals inoculated with guinea pig cytomegalovirus (GPCMV). These animals all became deaf eight days after inoculation into the perilymphatic compartment and showed severe inflammatory changes within the inner ear. Animals that received inactivated virus maintained their hearing throughout the observation period and exhibited normal cochlear morphology. Neither group had serum or perilymph antibody to GPCMV eight days after viral inoculation. We then investigated the effect of systemic immunity to GPCMV on inner ear viral challenge in animals with high levels of serum antibodies to GPCMV. No significant hearing loss could be detected eight days after inner ear inoculation. Seropositive animals that received live virus demonstrated a significant rise in perilymph antibody titer to GPCMV and showed preservation of normal cochlear morphology. Thus, systemic and inner ear immunity to GPCMV afforded protection against damage caused after direct perilymphatic inoculation of live virus.

Action Potentials↗

Energy dispersive x-ray analysis of inner ear fluids and tissues during the ontogeny of cochlear function.

Energy dispersive x-ray analysis (EDXA) was used to characterize freeze-dried, microdissected samples of inner ear fluids and tissues from neonatal gerbils throughout the period of cochlear functional development, between 10 and 18 days after birth. EDXA spectra from endolymph residue demonstrated that the adult ionic composition of this fluid is established before functional onset, and before the appearance of the endocochlear potential. However, stria vascularis spectra showed substantial increases in relative phosphorus and sodium content during the period in which auditory thresholds improve by approximately 100 dB, in which the endocochlear potential appears and increases to its adult value, and in which the level of metabolism of the stria increases dramatically. The increase in relative phosphorus content of stria in particular occurred with a time course which was very similar to, though slightly earlier than, that of the developmental increase in the endocochlear potential. It is concluded that increases in the relative phosphorus content of stria may represent increases in inorganic phosphate associated with strial metabolism. Increases in relative sodium content may reflect the action of an ion transport system which directs this element into strial cells during generation of the endocochlear potential.

Aging↗

Tonotopic organization in the central auditory pathway of the Mongolian gerbil: a 2-deoxyglucose study.

The uptake of 2-deoxyglucose (2-DG) was employed to map functional activation of the central auditory pathway in the mongolian gerbil, during 85 dB SPL stimulation with pure tonal stimuli at frequencies of 0.75, 3.0, or 12.0 kHz. Pure tones produced foci of very high 2-DG uptake, when compared to adjacent tissue, in the cochlear nucleus, superior olivary complex, and inferior colliculus. Less distinct areas of elevated 2-DG uptake were seen in the dorsal and ventral nuclei of the lateral lemniscus, medial geniculate nucleus, and auditory cortex. Little or no change in the distribution of 2-DG uptake was noted in the nucleus of the trapezoid body. The location of discrete regions of relatively high 2-DG uptake varied systematically with stimulus frequency. The tonotopic organization demonstrated by 2-DG mapping agreed well with the results of previous electrophysiological studies for most structures. However, in the inferior colliculus, stimulus-evoked increases in 2-DG uptake were found to occur in a fixed pattern of three to four bands across the central nucleus, which did not correspond to any previously reported anatomical or physiological organization. Pure tonal stimuli activated discrete portions of this banding pattern. Also, a small area at the ventromedial edge of the colliculus was more broadly tuned than other regions of the nucleus. It is concluded that 2-DG uptake is well suited to the investigation of tonotopic organization. This technique reveals patterns of activation which have not been observed with other methodologies.

Animals↗

Auditory stimulation alters the pattern of 2-deoxyglucose uptake in the inner ear.

The 2-deoxy-D-glucose (2-DG) autoradiographic technique was adapted for application to the inner ear. The uptake of [14C]-DG during silence was compared with that observed during exposure to wide band noise (WBN) or pure tones at an intensity level of 85 db SPL. In silence, the highest levels of 2-DG uptake were observed in the spiral ligament, spiral prominence and stria vascularis, with approximately equal levels of uptake in each structure. The high levels of 2-DG uptake observed in the ligament and prominence are surprising, and suggest a more active role for these structures in cochlear function than has previously been suspected. Levels of uptake in the organ of Corti, spiral ganglion and VIIIth nerve were much lower, although well above background. During exposure to WBN, 2-DG uptake increased markedly in the VIIIth nerve, and spiral ganglion throughout the cochlea, and in the organ of Corti in the lower basal turn. 2-DG uptake did not change significantly in the spiral ligament or stria vascularis. During pure tone exposure, increased 2-DG uptake was noted in localized regions of the VIIIth nerve and spiral ganglion.

Animals↗

Functional ontogeny in the central auditory pathway of the Mongolian gerbil. A 2-deoxyglucose study.

The 2-deoxyglucose (2-DG) autoradiographic technique was used to map functional activity in the central auditory system of the mongolian gerbil, throughout the period of functional onset. Uptake of 2-DG during exposure to 105 dB SPL wide band noise (WBN) was compared to silence in adults and in neonates at 12, 14, 16 and 18 days after birth (DAB). At 12 DAB, WBN exposure increased 2-DG uptake relative to silence only in the ventral cochlear nucleus. At 14 DAB, 2-DG uptake increased during WBN in the entire cochlear nuclear complex, superior olivary complex, and ventral nucleus of the lateral lemniscus. These stimulus-evoked increases in 2-DG uptake were at adult levels. However, little or no stimulus-evoked increase was seen in higher auditory nuclei at 14 DAB. By 16 DAB, 2-DG uptake also increased during WBN exposure in the dorsal nucleus of the lateral lemniscus, inferior colliculus and medial geniculate nucleus. By 18 DAB, WBN exposure produced increases in 2-DG uptake of medullary and pontine auditory nuclei which exceeded those seen in adults. At higher levels of the pathway, increases were comparable to those seen in adults. WBN-induced increases in 2-DG uptake observed in the cochlear nuclear and superior olivary complexes of neonates were comparable in all regions at all ages, even at 12 DAB. However, the 2-DG uptake increases observed at 16 and 18 DAB were appreciably greater in those regions of the inferior colliculus and medial geniculate nucleus which respond to high frequencies.

Aging↗

Increasing intensities of wide band noise increase [14C]2-deoxyglucose uptake in gerbil central auditory structures.

The [14C]2-deoxyglucose (2DG) technique has been used to map the effects of increasing intensities of wide band noise on 2DG uptake in mongolian gerbil brain auditory structures. Animals were injected with [14C]2DG and exposed to silence or continuous wide band noise at 25 dB, 45 dB, 65 dB, 85 dB or 105 dB SPL. Brains were removed, frozen-sectioned and autoradiographed on X-ray film. The ratio of the optical density of gray matter structures to the optical density of cerebellar peduncles in each animal was used to semiquantitate the results. The dorsal and ventral cochlear nuclei, superior olive/trapezoid body, inferior colliculus, and the dorsal and ventral nuclei of the lateral lemniscus all showed increases in 2DG uptake during exposure to wide band noise (WBN). As noise intensity increased from 0 to 105 dB SPL, 2DG uptake increased regularly to a maximum at 85 or 105 dB SPL. As WBN intensity increased, deeper layers of inferior colliculus were activated. The medial geniculate nucleus and auditory cortex showed a lesser increase in 2DG uptake during noise exposure. Non-auditory structures, including the cerebellar cortex and the medullary reticular nuclei, showed no increase in 2DG uptake during noise exposure at any intensity tested.

Animals↗

Neural phase-locking properties in the absence of cochlear outer hair cells.

A combined regimen of kanamycin sulfate treatment (175 mg/kg/day) and behavioral evaluation of resulting audiometric threshold shifts was used to produce selective outer hair cells (OHC) loss in chinchillas. This protocol resulted in a 3-7 mm region in the cochlear base in which OHCs were completely absent and inner hair cells (IHCs) were largely resent and normal at both light and electron microscopic levels. Partial OHC loss was associated with audiometric threshold shifts in excess of 15 dB, while complete OHC loss was associated with audiometric threshold shifts in excess of 40 dB. After recovery periods of at least three weeks, phase-locking was examined across frequency for auditory nerve (VIIIth nerve) and ventral cochlear nucleus (VCN) neurons. The frequency range for neural phase-locking in normal subjects extended up to approximately 4 kHz for VIIIth nerve fibers and 3 kHz for VCN neurons. Following kanamycin intoxication, however, the frequency range for neural phase-locking in both of these auditory regions varied with characteristic frequency (CF): neurons whose CF corresponded to normal cochlear regions exhibited phase-locking throughout the normal frequency range; neurons whole CF corresponded to cochlear regions with selective OHC loss exhibited a marked reduction in the frequency range over which they could phase-lock.

Animals↗

Precise extracellular marking in the auditory nerve with high impedance micropipettes.

A procedure is described which permitted for the first time accurate marking of the recording sites of primary auditory nerve fibers, peripheral to their entrance into the brainstem. The technique, which involves a modification of the fast green FCF dye marking procedure, does not interfere with the recording quality of the high-impedance micropipettes, requires no special histology, permits routine production od 5-15 micron diameter marks at extracellular recording sites, and employs a dye known to be noncytotoxic.

Animals↗

Ultrastructural correlates of selective outer hair cell destruction following kanamycin intoxication in the chinchilla.

Kanamycin ototoxicity, combined with behavioral audiometry to evaluate threshold shifts, was used to destroy outer hair cells (OHCs) in the basal cochlea of the chincilla while leaving the inner hair cell (IHC) population largely intact. After survival times of four weeks to one year, transmission electron microscopy was employed to determine the condition of surviving hair cells and neural elements. Throughout the region of OHC loss, IHCs and their innervation were normal in appearance if their adjacent supporting cells were undamaged. When IHC supporting cells, specifically the inner pillar cells, were damaged or absent, damage to IHCs was commonly observed. Such supporting cell-related damage included extrusion of the cuticular plate from the surface of the reticular lamina, encapsulation and/or fusion of stereocilia, and gross distortion of hair cell shape. When the outer supporting cells of the organ of Corti were undamaged following OHC loss, outer spiral fibers were found to have survived in near-normal numbers in the region from 0.5-1.0 mm basal to the basal most surviving OHC, but suffered progressive attrition toward the basal end of the cochlea. It is concluded that kanamycin-induced OHC loss can occur without concommitant IHC damage or outer spiral fiber loss.

Animals↗

Prenatal experience and avian development: brief auditory stimulation accelerates the hatching of Japanese quail.

A single 2-hour exposure to auditory stimulation at any point during the final 3 days of incubation accelerates the hatching of Japanese quail. The 3-day sensitive period includes both prenatal and perinatal stages of incubation. So far as is known these results provide the first unequivocal evidence that short-term prenatal sensory stimulation can affect the development of an avian embryo.

Acoustic Stimulation↗

Experimental congenital cytomegalovirus labyrinthitis and sensorineural hearing loss.

Cytomegalovirus is a leading cause of human congenital viral infection and hearing loss. The pathogenesis of human congenital cytomegalovirus infection is poorly understood. We have developed a reproducible model of congenital cytomegalovirus-induced sensorineural hearing loss in guinea pigs. This report reviews our previously published results and provides additional new information about this model.

Animals↗

Elaboration of systemic immunity following inner ear immunization.

The development of systemic humoral and cellular immunity following antigen presentation in the inner ear was compared with that seen following middle ear and peritoneal inoculation routes. Antibody developing against keyhole limpet hemocyanin was measured by a sensitive enzyme-linked immunofiltration assay, and cell-mediated immunity was measured by in vitro lymphocyte blastogenesis. The inner ear and peritoneal routes of antigen presentation resulted in a parallel rise in antibody over a 3-week period. In contrast, the middle ear route resulted in a weak, transient antibody response by 2 weeks. The acquisition of cell-mediated immunity occurred earliest (day 14) in the group receiving antigen intraperitoneally. A significant but smaller proliferative response was also seen in the group receiving antigen via the inner ear route on days 14 and 21. In contrast, the middle ear route failed to result in cell-mediated immunity. These studies indicate that the inner ear is an effective route of antigen processing which results in the acquisition of systemic humoral and cellular immunity. The development of systemic immunity, in turn, has been found to be protective of the inner ear.

Animals↗

A reexamination of experimental type II collagen autoimmunity: middle and inner ear morphology and function.

Type II collagen autoimmunity has been reported to result in a number of middle and inner ear morphological and functional abnormalities. We investigated the immunological, electrophysiological, and anatomical effects of this autoimmune state in well-established Wistar-Furth rat models of type II collagen autoimmune arthritis. Seventeen animals immunized with bovine type II collagen were divided into short term (1-3 months postimmunization) and long term (9-11 months) groups. Thirty-three experimental ears were tested electrophysiologically and were compared to nine ears of unimmunized Wistar-Furth rats. No hearing loss was found in the immunized animals, except for four animals that showed middle ear abscess formation consistent with spontaneous, purulent otitis media. All immunized animals showed very significant serum and perilymph antibody titers to type II collagen. No morphological abnormalities of the external, middle, or inner ears could be identified in the noninfected experimental animals. These findings do not support previously reported observations that type II collagen autoimmunity results in ear disease.

Animals↗