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Biomedical subjects

A F Ryan

Publications and source records attributed to A F Ryan.

At least 109 records · Page 6Linked to original sources

Amino acid labeling patterns in the efferent innervation of the cochlea: an electron microscopic autoradiographic study.

Light microscopic autoradiography and electron microscopic autoradiography were used to study the distribution of label in the cochlear efferents following in vivo incubation with tritiated amino acids. Two basic patterns of labeling were observed. These patterns correspond closely to the lateral and medial superior olivary complex (SOC) olivocochlear systems identified by Warr and Guinan ('79, Brain Res. 173:152-155). Our electron microscopic observations suggest that, at least in the gerbil, the complete separation of outer hair cell (OHC) versus inner hair cell (IHC) efferent innervation proposed by these investigators based upon light microscopic data does not occur. Rather, our data suggest that while the lateral SOC system supplies endings only to the region under the IHC, the medial SOC system may supply endings beneath both the IHCs and OHCs.

Amino Acids↗

The effect of complement depletion on immunologically mediated middle ear effusion and inflammation.

Immunologic injury during immune response to antigen in the middle ear cavity has been suggested to be a contributing factor in otitis media with effusion (OME). One of the mechanisms proposed involves the generation of immune complexes, with subsequent injury mediated by complement fixation. To evaluate the potential role of complement in OME, an animal model of immune-mediated middle ear effusion and inflammation was used. Antigenic challenge of the middle ear of normal, sensitized guinea pigs results in OME. This response was compared with that observed in guinea pigs whose sera were decomplemented by treatment with cobra venom factor. As compared to controls, decomplemented animals exhibited less effusion [130 (+/- 35) vs 83 (+/- 60) microliter, P less than 0.05] and inflammation in the middle ear following antigenic challenge. These results suggest that complement could play a role in the pathogenesis of OME. However, the fact that animals with severely depleted serum complement still displayed a moderate amount of effusion and inflammation indicates that other mechanisms are also involved in our model of immune-mediated OME.

Animals↗

Development of mammalian endocochlear potential: normal ontogeny and effects of anoxia.

The development of the positive endocochlear potential (EP), the negative anoxic EP, and the organ of Corti potential were measured at various postnatal ages in the Mongolian gerbil, beginning at 8 days after birth (DAB). The organ of Corti potential (OCP) was present at 8 DAB but averaged 21% less than the adult value. OCP increased regularly with age, reaching adult values of -90 mV by 14 DAB. The positive EP was first observed at 10 DAB, at which age it averaged only 2-3 mV. This potential increased monotonically between 10 and 20 DAB, by which time it had reached the adult value of 75 mV. Anoxia did not result in a negative EP until 12 DAB, at which age this potential averaged -7 mV. The negative anoxic EP matured more rapidly than the positive EP, achieving the adult value of 40 mV by 18 DAB. During development the positive EP appeared to closely parallel the maturation of glucose metabolism in the stria vascularis. The negative anoxic EP was more closely related temporally to the development of cochlear microphonic potential (CM) thresholds. It is hypothesized that changes which occur between 10 and 16 DAB in the apical membranes of the cochlear hair cells contribute to the maturation of both CM and the negative anoxic EP.

Animals↗

Ventral cochlear nucleus neural discharge characteristics in the absence of outer hair cells.

The role of the cochlear outer hair cell (OHC) in auditory processing remains poorly understood. The OHCs possess an independent afferent innervation which constitutes 5-10% of cochlear afferent neurons and which appears to project to the cochlear nucleus (CN). Whether the OHCs contribute to the processing of auditory signals in the CN has not been determined. To address this question, kanamycin ototoxicity was used to produce selective OHC loss while leaving the inner hair cell (IHC) population largely intact, in the basal portion of the cochlea of chinchillas. Single unit responses were then recorded in the ventral cochlear nucleus (VCN), and compared to responses in untreated subjects. Many of the changes observed in VCN neural responses reflected changes which have previously been reported in the VIIIth nerve. However, frequency tuning curve tip segments which were normal in both bandwidth and length were observed in approximately 22% of the units associated with regions of complete OHC loss and preservation of IHCs. This has not been reported in previous OHC lesion studies. Also, first spike latency was found to be significantly lengthened for units associated with the OHC free regions. Those features of VCN neural responses which first arise within the CN, such as non-primary-like post-stimulus-time histogram response patterns, were unaffected by OHC loss. These results suggest that afferent fibers associated with OHCs do not play a major role in signal processing in the VCN.

Animals↗

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↗

Preferential glutamine uptake by cochlear hair cells: implications for the afferent cochlear transmitter.

The cochlear uptake of amino acids which are putative neurotransmitters, or closely-related compounds, was examined autoradiographically in the gerbil. Hair cells showed no preferential uptake of most compounds tested. However, preferential accumulation of glutamine by cochlear hair cells was striking. Vestibular hair cells showed no affinity for this amino acid. Glutamine uptake by cochlear hair cells may play an important role in afferent synaptic transmission, by providing transmitter precursor and/or by clearing the synaptic cleft.

Afferent Pathways↗

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↗

Effects of reaction time performance on single-unit activity in the central auditory pathway of the rhesus macaque.

The activity of single units at various locations in the central auditory pathway of rhesus macaques was recorded during the monkeys' performance and nonperformance in an auditory reaction time task. Evoked unit responses during performance were compared with those observed during passive delivery of identical stimuli. Single units were recorded from the cochlear nucleus, superior olivary complex, lateral lemniscus, inferior colliculus, medial geniculate nucleus, and auditory cortex. Significant effects of task performance on unit discharge patterns were observed at all levels of the central auditory pathway: Spontaneous discharge rates in the more peripheral auditory nuclei tended to be higher during performance. Evoked discharge that occurred relatively late during a stimulus presentation (greater than 75 msec after stimulus onset) was increased during performance, compared with the nonperformance condition, in nuclei above the cochlear nucleus. The initial latency of evoked discharge was increased during performance for subcortical nuclei but was decreased for units in auditory cortex. These results suggest that the effects of performance may be mediated by a tonic increase in the excitability of auditory units which operates primarily at peripheral auditory stations, and a descending, stimulus-evoked increase in excitability which primarily influences the cells of higher auditory nuclei. At the cortical level, these changes lead to increased signal-to-noise ratio of the evoked response during performance in the auditory task.

Acoustic Stimulation↗

The relationship of local cerebral glucose utilization to optical density ratios.

The validity of optical density ratios used in [14C]2-deoxyglucose neuroanatomical mapping experiments is evaluated by comparing local cerebral glucose utilization (LCGU) and optical density (OD) ratios in the same animals. OD ratios are calculated by dividing the optical density of different gray matter structures by the optical density of a single white matter structure in each animal. OD ratios are linearly related to LCGU within a given animal including stimulated, highly activated regions. Anesthesia profoundly affects the relationship between LCGU and OD ratios, however, showing that OD ratios do not provide an accurate index of LCGU between animals in different physiological states. Anesthesia had only a slight effect on OD ratios, however, indicating that OD ratios may be helpful in assessing whether structures are functionally activated between animals in different physiological states.

Animals↗

Preferential amino acid uptake identifies Type II spiral ganglion neurons in the gerbil.

The localization of 3H-labeled amino acids was compared by light and electron microscopic autoradiography in the spiral ganglion of the gerbil, following in vivo intracochlear incubations. Following incubations with taurine, a population of heavily labeled neurons could be distinguished from lightly labeled neurons. The heavily labeled population comprised 5-6% of spiral ganglion neurons, and included the least myelinated cells. Ultrastructurally, the heavily labeled neurons were characterized by a loosely coiled Schwann cell sheath covering the cell body, and the presence of abundant cytoplasmic microfilaments. The unlabeled cells showed a typical perikaryal myelin sheath and cytoplasm rich in rough endoplasmic reticulum. It is concluded that the spiral ganglion of the gerbil contains both Type I and Type II neurons, and that Type II neurons preferentially incorporate the amino acid taurine. Type II neurons are therefore biochemically as well as morphologically distinct from Type I neurons.

Amino Acids↗

Differential labeling of sensory cell and neural populations in the organ of Corti following amino acid incubations.

Label localization was compared by light and electron microscopic autoradiography in the organ of Corti of the gerbil, following in vivo incubation with one of eight 3H-labeled amino acids. Following incubation with GABA, efferent endings underneath the outer hair cells were heavily labeled, as were all tunnel crossing fibers, many small fibers in the inner spiral bundle and some efferents beneath the inner hair cells. This pattern was absent following incubations with the GABA analog muscimol. Following L- and especially D-aspartic acid incubations, efferent endings under the inner hair cells and small fibers of the inner spiral bundle were preferentially labeled. It is concluded that these differential labeling patterns after GABA and aspartic acid incubations reflect two populations of efferent fibers in the organ of Corti: one terminating primarily upon the outer hair cells and one underneath the inner hair cells. Cochlear hair cells showed the highest level of labeling following incubation with alanine. Inner hair cells were more heavily labeled than outer hair cells following incubations with alanine and glycine. Hair cell labeling was comparable to that of supporting cells for most amino acids. However, for alanine and glycine the labeling of inner hair cells, and for L-aspartic and glutamic acid the labeling of all hair cells, was higher than that of structural cells. Labeling of hair cells was substantially lower than that of structural cells following taurine incubations.

Amino Acids↗

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↗