Biomedical subjects

P A Leake

Publications and source records attributed to P A Leake.

At least 19 recordsLinked to original sources

PubMed2001

Does exogenous GM1 ganglioside enhance the effects of electrical stimulation in ameliorating degeneration after neonatal deafness?

This study examined the combined effects of administration of exogenous GM1 ganglioside and electrical stimulation on the cochlear nucleus (CN) of cats deafened neonatally by ototoxic drugs. Five normal hearing adult cats served as controls. Another 12 cats were deafened bilaterally by daily injections of neomycin sulfate (60 mg/kg) for 17-21 days after birth until auditory brainstem testing demonstrated profound hearing loss. Six of the deaf animals comprised the GM1 group, which received daily injections of GM1 ganglioside (30 mg/kg) for 28-38 days during the period after profound deafness was confirmed, and prior to receiving a cochlear implant. The non-GM1 group (n=6) received no treatment during this interim period. All the deafened animals underwent unilateral cochlear implantation at 6-9 weeks postnatal and received several months (mean duration, 32 weeks) of chronic electrical stimulation (4 h/day, 5 days/week). Stimulation was delivered by intracochlear bipolar electrodes, using electrical signals that were designed to be temporally challenging to the central auditory system. Results showed that in the neonatally deafened animals, both the GM1 and non-GM1 groups, the volume of the CN was markedly reduced (to 76% of normal), but there was no difference between the animals that received GM1 and those that did not. The cross sectional areas of spherical cell somata in both GM1 and non-GM1 groups also showed a highly significant reduction in size, to < or =75% of normal after neonatal deafening. Moreover, in both the GM1 and non-GM1 groups, the spherical cells in the CN ipsilateral to the implanted cochlea were significantly larger (6%) than cells in the control, unstimulated CN. Again, however, there was no significant difference between the GM1 group and the non-GM1 group in spherical cell size. These results contrast sharply with previous reports that exogenous GM1 prevents CN degeneration after neonatal conductive hearing loss and partially prevents spiral ganglion cell degeneration when administered immediately after ototoxic drug deafening in adult animals. Taken together, findings to date suggest that GM1 may be effective in preventing degeneration only if the GM1 is administered immediately at the time hearing loss occurs.

Animals↗

PubMed2001

The effect of electrode configuration and duration of deafness on threshold and selectivity of responses to intracochlear electrical stimulation.

This report examines the effects of intracochlear electrode configuration and mode of stimulation (bipolar or monopolar) on neural threshold and spatial selectivity in the inferior colliculus (IC) of the cat. Single and multiunit IC recordings were made in three groups of animals; acutely deafened adults (controls), neonatally deafened animals studied at 6 to 18 months of age and neonatally deafened cats studied at 2.5 to 6.5 years. Response thresholds were plotted versus IC depth to measure the spatial distribution of responses. The response selectivity for each stimulating configuration was defined as the width of the resulting spatial tuning curve (STC) measured at 6 dB above threshold. Spiral ganglion cell (SG) survival was examined histologically in all neonatally deafened animals and correlated with physiological results. Animals studied at less than 1.5 years had SG densities of 23.5%-64.4% of normal (mean=42.7%) while animals studied at greater than 2.5 years had densities of 5.1%-18.3% of normal (mean=9.9%). Electrophysiological results include the following. (1) Monopolar thresholds were 7-8 dB lower than bipolar thresholds in the same animals. (2) Varying the configuration of bipolar contacts (measured as radial, offset radial and longitudinal pairs) did not systematically affect IC threshold in either controls or short-term neonatally deafened animals. In contrast, the long-term neonatally deafened animals showed a difference in threshold with each configuration. (3) The spatial distributions (Q(6 dB)) of responses to bipolar stimulation were approximately 40% more restricted than those for monopolar stimulation. (4) The spatial selectivity of neonatally deafened animals studied at ages up to 1.5 years was equal to that of control animals with normal auditory experience. However, selectivity was degraded in the older animals. (5) Selectivity was decreased in some animals with the longitudinal bipolar configuration and multiple response peaks were seen in several cases using this stimulus configuration.

Animals↗

PubMed2000

Plasticity in central representations in the inferior colliculus induced by chronic single- vs. two-channel electrical stimulation by a cochlear implant after neonatal deafness.

The goal of this research is to examine the functional consequences of patterned electrical stimulation delivered by a cochlear implant in the deafened developing auditory system. In previous electrophysiological experiments conducted in the inferior colliculus (IC), we have demonstrated that the precise cochleotopic organization of the central nucleus (ICC) develops normally in neonatally deafened unstimulated cats and is unaltered despite the lack of normal auditory input during development. However, these studies also showed that chronic electrical stimulation delivered at a single intracochlear location by one bipolar channel of a cochlear implant induces significant expansion of the central representation of the stimulated cochlear sector and degrades the cochleotopic organization of the IC. This report presents additional data from a new experimental series of neonatally deafened cats that received chronic stimulation on two adjacent bipolar intracochlear channels of a cochlear implant. Results suggest that competing inputs elicited by electrical stimulation delivered by two adjacent channels can maintain the selective representations of each activated cochlear sector within the central auditory system and prevent the expansion seen after single-channel stimulation. Alternating stimulation of two channels and use of highly controlled electrical signals may be particularly effective in maintaining or even sharpening selectivity of central representations of stimulated cochlear sectors. In contrast, simultaneous stimulation using two channels of a model analog cochlear implant processor in one experimental animal failed to maintain channel selectivity and resulted in marked expansion and fusion of the central representations of the stimulated channels. This potentially important preliminary result suggests that under some conditions the central auditory system may be unable to discriminate simultaneous, overlapping inputs from adjacent cochlear implant channels as distinct.

Animals↗

PubMed2000

Electrical cochlear stimulation in the deaf cat: comparisons between psychophysical and central auditory neuronal thresholds.

Cochlear prostheses for electrical stimulation of the auditory nerve ("electrical hearing") can provide auditory capacity for profoundly deaf adults and children, including in many cases a restored ability to perceive speech without visual cues. A fundamental challenge in auditory neuroscience is to understand the neural and perceptual mechanisms that make rehabilitation of hearing possible in these deaf humans. We have developed a feline behavioral model that allows us to study behavioral and physiological variables in the same deaf animals. Cats deafened by injection of ototoxic antibiotics were implanted with either a monopolar round window electrode or a multichannel scala tympani electrode array. To evaluate the effects of perceptually significant electrical stimulation of the auditory nerve on the central auditory system, an animal was trained to avoid a mild electrocutaneous shock when biphasic current pulses (0.2 ms/phase) were delivered to its implanted cochlea. Psychophysical detection thresholds and electrical auditory brain stem response (EABR) thresholds were estimated in each cat. At the conclusion of behavioral testing, acute physiological experiments were conducted, and threshold responses were recorded for single neurons and multineuronal clusters in the central nucleus of the inferior colliculus (ICC) and the primary auditory cortex (A1). Behavioral and neurophysiological thresholds were evaluated with reference to cochlear histopathology in the same deaf cats. The results of the present study include: 1) in the cats implanted with a scala tympani electrode array, the lowest ICC and A1 neural thresholds were virtually identical to the behavioral thresholds for intracochlear bipolar stimulation; 2) behavioral thresholds were lower than ICC and A1 neural thresholds in each of the cats implanted with a monopolar round window electrode; 3) EABR thresholds were higher than behavioral thresholds in all of the cats (mean difference = 6.5 dB); and 4) the cumulative number of action potentials for a sample of ICC neurons increased monotonically as a function of the amplitude and the number of stimulating biphasic pulses. This physiological result suggests that the output from the ICC may be integrated spatially across neurons and temporally integrated across pulses when the auditory nerve array is stimulated with a train of biphasic current pulses. Because behavioral thresholds were lower and reaction times were faster at a pulse rate of 30 pps compared with a pulse rate of 2 pps, spatial-temporal integration in the central auditory system was presumably reflected in psychophysical performance.

Age Factors↗

PubMed2000

Responses of inferior colliculus neurons to amplitude-modulated intracochlear electrical pulses in deaf cats.

Current cochlear prostheses use amplitude-modulated pulse trains to encode acoustic signals. In this study we examined the responses of inferior colliculus (IC) neurons to sinusoidal amplitude-modulated pulses and compared the maximum unmodulated pulse rate (Fmax) to which they responded with the maximum modulation frequency (maxFm) that they followed. Consistent with previous results, responses to unmodulated pulses were all low-pass functions of pulse rate. Mean Fmax to unmodulated pulses was 104 pulses per second (pps) and modal Fmax was 60 pps. Above Fmax IC neurons ceased responding except for an onset burst at the beginning of the stimulus. However, IC neurons responded to much higher pulse rates when these pulses were amplitude modulated; 74% were relatively insensitive to carrier rate and responded to all modulated carriers including those exceeding 600 pps. In contrast, the responses of these neurons (70%) were low-pass functions of modulation frequency, and the remaining (30%) had band-pass functions with a maxFm of 42 and 34 Hz, respectively. Thus temporal resolution of IC neurons for modulated frequencies is significantly lower than that for unmodulated pulses. These two measures of temporal resolution (Fmax and maxFm) were uncorrelated (r(2) = 0.101). Several parameters influenced the amplitude and temporal structure of modulation responses including modulation depth, overall intensity and modulation-to-carrier rate ratio. We observed distortions in unit responses to amplitude-modulated signals when this ratio was 1/4 to 1/6. Since most current cochlear implant speech processors permit ratios that are significantly greater than this, severe distortion and signal degradation may occur frequently in these devices.

Animals↗

PubMed1999

Chronic electrical stimulation by a cochlear implant promotes survival of spiral ganglion neurons after neonatal deafness.

This investigation examined the consequences of neonatal deafness and chronic intracochlear electrical stimulation delivered by a cochlear implant during maturation. Kittens were bilaterally deafened by an ototoxic drug administered daily for 2 weeks immediately after birth. Unilateral electrical stimulation was initiated at 7-10 weeks of age and continued over periods of 22-47 weeks (4 hours/day; 5 days/week). Bipolar intracochlear electrodes delivered one of several different electrical signals designed to be temporally challenging to the central auditory system. Morphometric evaluation of spiral ganglion (SG) cell somata within Rosenthal's canal demonstrated a mean of approximately 50% of normal cell density maintained in the chronically stimulated ears, compared with approximately 30% on the control deafened side. This 20% difference in density was highly significant and was greater than differences reported in earlier studies using 30 pps stimulation delivered by either intracochlear bipolar or round window monopolar electrodes. However, the duration of stimulation was also longer in the present study, so it is unclear to what extent the nature of the temporally challenging stimulation vs. its duration contributed to the marked increase in survival. Measurements of the SG cell somata revealed a pronounced decrease in cell diameter in neonatally deafened cats studied about 1 year after deafening, and an additional decrease after long-term deafness (2.5-6.5 years). Furthermore, in the cochlear regions with the greatest stimulation-induced differences in SG cell density, direct measurements of cross-sectional soma area of the largest cells revealed that cells were significantly larger in the stimulated ears. Thus, in addition to the marked increase in the number of surviving SG cells, larger soma area contributed modestly to the pronounced increase in neural density following chronic electrical stimulation.

Animals↗

PubMed1999

Postnatal development of the organ of Corti in cats: a light microscopic morphometric study.

This study quantitatively characterizes the development of the major morphological features of the organ of Corti during the first 2 weeks postnatal, the period when the cat auditory system makes the transition from being essentially non-functional to having nearly adult-like responses. Four groups of kittens (n = 3) were studied at one day postnatal (P1), P5, P10, P15, and compared to adults. Measurements were made of the organ of Corti at 3 cochlear locations: 20%, 60% and 85% of basilar membrane length from the base cochlear locations which in the adult correspond to best frequencies of approximately 20 kHz, 2 kHz and 500 Hz, respectively. In addition, measurements of basilar membrane length and opening of the tunnel of Corti were made in 20 cochlear specimens from kittens aged P0-P6. Results indicate that: (i) at P0 the basilar membrane has attained adult length, and the tunnel of Corti is open over approximately the basal one-half of the cochlea; (ii) the initial opening of the tunnel of Corti occurs at a site about 4 mm from the cochlear base (best frequency of approximately 25 kHz in the adult cochlea); (iii) the thickness of the tympanic cell layer decreases markedly at the basal 20-kHz location; (iv) the areas of the tunnel of Corti and space of Nuel and the angulation of the inner hair cells (IHC) relative to the basilar membrane all show marked postnatal increases at both the middle and apical locations; (v) IHC are nearly adult-like in length and shape at birth, whereas the OHC (at 2-kHz and 500-Hz locations) undergo marked postnatal changes; (vi) disappearance of the marginal pillars and maturation of the supporting cells are not yet complete by P15.

Animals↗

PubMed1999

Temporal properties of chronic cochlear electrical stimulation determine temporal resolution of neurons in cat inferior colliculus.

As cochlear implants have become increasingly successful in the rehabilitation of adults with profound hearing impairment, the number of pediatric implant subjects has increased. We have developed an animal model of congenital deafness and investigated the effect of electrical stimulus frequency on the temporal resolution of central neurons in the developing auditory system of deaf cats. Maximum following frequencies (Fmax) and response latencies of isolated single neurons to intracochlear electrical pulse trains (charge balanced, constant current biphasic pulses) were recorded in the contralateral inferior colliculus (IC) of two groups of neonatally deafened, barbiturate-anesthetized cats: animals chronically stimulated with low-frequency signals (< or = 80 Hz) and animals receiving chronic high-frequency stimulation (> or = 300 pps). The results were compared with data from unstimulated, acutely deafened and implanted adult cats with previously normal hearing (controls). Characteristic differences were seen between the temporal response properties of neurons in the external nucleus (ICX; approximately 16% of the recordings) and neurons in the central nucleus (ICC; approximately 81% of all recordings) of the IC: 1) in all three experimental groups, neurons in the ICX had significantly lower Fmax and longer response latencies than those in the ICC. 2) Chronic electrical stimulation in neonatally deafened cats altered the temporal resolution of neurons exclusively in the ICC but not in the ICX. The magnitude of this effect was dependent on the frequency of the chronic stimulation. Specifically, low-frequency signals (30 pps, 80 pps) maintained the temporal resolution of ICC neurons, whereas higher-frequency stimuli significantly improved temporal resolution of ICC neurons (i.e., higher Fmax and shorter response latencies) compared with neurons in control cats. Furthermore, Fmax and latencies to electrical stimuli were not correlated with the tonotopic gradient of the ICC, and changes in temporal resolution following chronic electrical stimulation occurred uniformly throughout the entire ICC. In all three experimental groups, increasing Fmax was correlated with shorter response latencies. The results indicate that the temporal features of the chronically applied electrical signals critically influence temporal processing of neurons in the cochleotopically organized ICC. We suggest that such plastic changes in temporal processing of central auditory neurons may contribute to the intersubject variability and gradual improvements in speech recognition performance observed in clinical studies of deaf children using cochlear implants.

Acoustic Stimulation↗

PubMed1997

Topography of spiral ganglion projections to cochlear nucleus during postnatal development in cats.

A fundamenntal organizational principle of the central auditory system is that virtually all areas are tonotopically organized. However, we know very little about the timing or mechanisms that are responsible for the development of this organization. When cats are born, their auditory nervous systems are extremely immature, and their hearing thresholds are very high. Until postnatal days 7-10 (P7-10), cats have behavioral and physiological thresholds which are near or above the pain threshold for adults and also have poor frequency selectivity. Physiological thresholds for auditory nerve fibers and cochlear nucleus neurons are typically above 100-120 dB SPL (sound pressure level re 20 microPa). Three weeks later (at approximately P31), the sensitivity and frequency discrimination (tuning) of these neurons approximate adult values. This study examines the development of the tonotopic projections from the spiral ganglion to the cochlear nucleus during the period in cat development in which the auditory system undergoes the transition from being essentially nonfunctional to having adult-like function. With the animals heavily anesthetized, the cochleas were surgically exposed in kittens ranging in age from P6 to P45. Focal injections of Neurobiotin (NB) were made into Rosenthal's canal, labeling a small cluster of cells in the spiral ganglion of each cochlea. The projections of these labeled cells were visualized as frequency-specific bands of labeled axons and terminals in all major subdivisions of the cochlear nucleus. The thickness of these bands (i.e., the dimension of the bands orthogonal to the isofrequency representation and across the frequency gradient) were measured and compared to similar projections in adults. As in adult cats, the thickness of the bands varied only slightly with the location of the injection site (frequency representation) over a range of 1-7 mm from the cochlear base (45-13 kHz). Moreover, band thickness did not vary significantly with age. These data indicate that the tonotopic organization of spiral ganglion projections to the cochlear nucleus is as precise in kittens as young as P6 as it is in adults.

Afferent Pathways↗

PubMed1997

Quantitative analysis of spiral ganglion projections to the cat cochlear nucleus.

A quantitative examination of the tonotopic organization of primary afferent projections to the cochlear nucleus (CN) in adult cats was conducted by using focal extracellular injections of Neurobiotin (NB) into the spiral ganglion of the basal cochlea. One to three injections separated by intervals of at least 2 mm were positioned along the basal one-third of the cochlea. Each injection produced discrete projection laminae that appeared as parallel horizontal sheets of labeled axons terminals distributed sequentially dorsally to ventrally across each major CN subdivision: the anteroventral, posteroventral, and dorsal cochlear nucleus, (AVCN, PVCN, and DCN, respectively). The length (rostrocaudal dimension), width (mediolateral dimension), thickness (dorsoventral dimension), and relative placement of 18 "frequency-band" laminae were measured in 10 adult cochlear nuclei. The average AVCN projection thickness was approximately twice that of the PVCN and DCN projections. In double injection cases, the center-to-center separation between AVCN laminae was also approximately twice that in the PVCN and equal to that in the DCN. Lamina thickness did not differ significantly as a function of frequency representation. However, in both width and length, mid-frequency laminae were up to two times larger than high-frequency laminae. Thus, the results indicate that DCN projections are the most discrete (i.e., are the thinnest and have the least overlap between adjacent frequency projections), whereas the AVCN projections are the largest but are as discrete as PVCN projections. In addition, high-frequency projections are smaller and more discrete than mild-frequency projections, which are larger and have greater overlap with adjacent frequency projections.

Animals↗

PubMed1997

Cochlear pathology induced by aminoglycoside ototoxicity during postnatal maturation in cats.

Cochlear pathology resulting from neonatal administration of the aminoglycoside antibiotic, neomycin sulfate, was studied in young kittens at 15-24 days postnatal. Hearing thresholds showed severe to profound hearing loss in all but one animal. Scanning electron microscopy demonstrated that initial hair cell degeneration occurred in the extreme base (hook region) of the cochlea and sequentially progressed to the basal, middle, then the apical coil of the cochlea. The first row of outer hair cells degenerated first, followed by row 2, then row 3; the last cells to degenerate in a given region were the inner hair cells. This pattern of hair cell degeneration is similar to that seen in adults with neomycin ototoxicity. In contrast, the spiral ganglion exhibited a different pattern of degeneration with initial cell loss occurring in the middle of the cochlea, about 40-60% from the base (approximately 2.8-8 kHz). Thus, neuronal degeneration apparently is not secondary to sensory cell loss, but rather comprises an independent process in these neonatal animals. Taken together, the findings suggest that the spiral ganglion cell loss in the middle cochlear turn results from increased aminoglycoside sensitivity associated with an earlier initial onset of function in these neurons as compared to other cochlear regions.

Animals↗

PubMed1995

Consequences of chronic extracochlear electrical stimulation in neonatally deafened cats.

This investigation examined the consequences of neonatal deafness and chronic electrical stimulation of the cochlea in the developing auditory system. Cats were bilaterally deafened by daily ototoxic drug administration for two weeks after birth. Electrical stimulation was initiated at 6-9 weeks of age and continued for up to 6 months, using monopolar round window electrodes that synchronously excited auditory neurons throughout the cochlea. Morphometric evaluation of the density of spiral ganglion cell somata within Rosenthal's canal demonstrated that chronic stimulation induced an increase of about 6% in neuronal survival. Although this difference was statistically significant, extracochlear stimulation in these cats was less effective in preventing neural degeneration than lower intensity, more restricted intracochlear stimulation that was shown in a previous study to induce an average increase of about 13% in neuronal survival. Electrophysiological recording experiments conducted in the inferior colliculus in these animals indicated that monopolar extracochlear stimulation can induce profound alterations in the spatial (frequency) selectivity of the auditory midbrain. On average, results were similar to those previously reported for bipolar intracochlear stimulation, showing about a two-fold expansion of the central representation of chronically stimulated electrodes. However, results with extracochlear stimulation showed much greater variability among individual animals. The results presented suggest that it is problematic to effect consistent 'whole' nerve stimulation using monopolar round window electrodes. Moreover, this mode of stimulation can induce profound functional alterations in the central nervous system and is substantially less effective in forestalling the degeneration of auditory neurons than intracochlear stimulation. Both these results contraindicate the implantation of such electrodes in young children for the purpose of maintaining the integrity of the auditory system for later application of a multichannel cochlear implant.

Animals↗

PubMed1994

Changes in the cat cochlear nucleus following neonatal deafening and chronic intracochlear electrical stimulation.

The effects of chronic intracochlear electrical stimulation on the cochlear nucleus (CN) were studied in eight cats that were neonatally deafened by daily intramuscular injections of neomycin. Profound hearing loss was confirmed in each animal by auditory brainstem response (ABR) and frequency following response (500 Hz) testing. Five of the kittens were implanted unilaterally with a scala tympani electrode array at ages 8-16 weeks. These kittens were stimulated daily for four hours at 2 dB above the evoked ABR threshold, over a period of three months, and subsequently euthanized for histological analysis at 26-32 weeks of age. The three remaining deaf kittens were maintained without stimulation over prolonged periods in order to study the long-term consequences of neonatal deafening, and were euthanized at 66-133 weeks of age. This study compares the CN of these deafened experimental animals and the CN of normal adult cats. Three experimental parameters were examined: CN volume, cross-sectional area of spherical cells in the rostral anteroventral cochlear nucleus (AVCN), and spherical cell density in this same region. The CN in animals that received electrical stimulation showed significant bilateral degenerative changes in all three measured parameters. Total nuclear volume was reduced by 35-36%, spherical cell size was reduced by 20-26%, and spherical cell density decreased by 36-42%, as compared to the normal cat CN. Comparisons were also made in the stimulated animals between CN ipsilateral to the stimulated cochlea and the contralateral, unstimulated CN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Spatial organization of inner hair cell synapses and cochlear spiral ganglion neurons.

The morphological organization of the central projections of the cat cochlear spiral ganglion into the cochlear nucleus was previously investigated by creating restricted lesions in the anteroventral cochlear nucleus (AVCN) to ablate selectively either the lateral or the medial aspect of isofrequency projection laminae. Such lesions resulted in highly selective retrograde degeneration of spiral ganglion cells. Ablation of the lateral part of the AVCN caused degeneration of cells within the scala tympani part of the ganglion, whereas medial ablations within the AVCN induced degeneration of the scala vestibuli aspect of the ganglion. The peripheral axons also degenerated and this fiber loss exhibited selective topographies that paralleled the cell loss within the spiral ganglion, although this phenomenon was more prominent in the proximal part of the osseous spiral lamina near the ganglion and less obvious more distally near the habenula perforata. In this investigation, inner hair cells (IHCs) from these selective lesion cases were evaluated by electron microscopy of serial sections through the basal synaptic regions. Results demonstrated differential degeneration of afferent synapses, with greater (but not completely selective) loss of pillar synapses after lateral AVCN lesions and greater loss of modiolar synapses after medial lesions. Because auditory nerve fibers of different spontaneous discharge rates (SRs) have different spatial distributions on the IHC (Liberman, Science 216:1239, 1982), our results suggest that this SR-based organization is maintained in a topographic organization across the vertical (scala tympani-to-scala vestibuli) dimension of the spiral ganglion cell cluster and carried into the ventral cochlear nuclei (VCN). Thus, in addition to the spiral frequency organization represented by the dorsal-to-ventral frequency map in the VCN, there is also an orderly organization of inputs from high- and low-SR fibers across the lateral-to-medial dimension of the VCN such that the lateral isofrequency laminae receive a proportionately greater input from high-SR fibers, whereas medial isofrequency laminae receive preferential input from low- and medium-SR fibers.

Animals↗

PubMed1992

Topographic organization of the cochlear spiral ganglion demonstrated by restricted lesions of the anteroventral cochlear nucleus.

The morphological organization of the central projections of the cat cochlear spiral ganglion into the cochlear nucleus has been investigated by creating restricted lesions in the anteroventral cochlear nucleus (AVCN) in order to ablate selectively either the lateral or the medial aspect of isofrequency projection laminae. Such lesions induced highly selective retrograde degeneration of spiral ganglion cells. Ablation of the lateral part of the AVCN resulted in degeneration of cells within the scala tympani portion of the ganglion, whereas medial lesions within the AVCN induced degeneration of the scala vestibuli portion of the ganglion. Since most, if not all, of the primary afferent axons of the cochlear nerve bifurcate into ascending and descending branches as they enter the brainstem, it is noteworthy that selective damage to the ascending branch in the AVCN was sufficient to induce retrograde degeneration of the spiral ganglion cell somata. The peripheral and central axons also degenerated, and the losses of both the radial nerve fibers in the osseous spiral lamina and the central axons passing into the modiolus displayed selective topographies that paralleled the cell loss within the spiral ganglion. The results of this study support our previous hypothesis, based upon earlier horseradish peroxidase labeling experiments, that there is a topographic organization to the projection of the spiral ganglion within the isofrequency laminae that is orthogonal to the frequency representation within the ventral cochlear nuclei (VCN). That is, in addition to the spiral frequency organization of the ganglion, represented by the dorsal-to-ventral frequency map in the VCN, there is also an orderly and sequential distribution of inputs from the vertical (scala tympani-to-scala vestibuli) dimension of the spiral ganglion across the lateral-to-medial axis of the VCN. The interaction of these two topographic representations, distributed across the three dimensions of the VCN, must partly define the selective and/or integrative neuronal response properties at this first level of central nervous system processing of auditory signals within the cochlear nuclei.

Animals↗

PubMed1992

Chronic intracochlear electrical stimulation in neonatally deafened cats: effects of intensity and stimulating electrode location.

An earlier study conducted in this laboratory suggested that chronic intracochelear electrical stimulation at moderate current levels can at least partially delay or prevent the retrograde degeneration of primary auditory (spiral ganglion) neurons that otherwise is progressive after neonatal deafness induced by ototoxic drug administration. Increased survival of spiral ganglion neurons was observed within the basal cochlear region near the stimulating biopolar electrode pairs, while in more apical regions there was no significant difference between the stimulated and control cochleas. The mechanisms underlying this maintenance of spiral ganglion neurons induced by chronic electrical stimulation are uncertain, especially since increased neuronal survival was observed over broader sectors of the ganglion than would be expected to be directly activated by the bipolar electrodes and moderate stimulation intensity (6 dB above electrically evoked auditory brainstem response threshold) used. In this report, data are presented from a second series of neonatally deafened and chronically stimulated cats. The parameters for chronic electrical stimulation were manipulated in two simple ways. First, the intensity of the electrical stimulus was reduced from the earlier study, while the duration of chronic stimualtion periods was increased; and secondly, two different intracochlear positions of stimulating electrodes were employed in different experimental groups. Results indicate that elecrical stimulation of the cochlea at an extremely low intensity (2 dB above electrically evoked auditory brainstem response threshold) is sufficient to at least partially prevent or delay ganglion cell degeneration in the deafened cochlea. In addition, data suggest a differential distribution of the maintained or conserved ganglion cells, such that when the stimulating electrode pair was positioned near the base of the cochlea increased ganglion survival in a more basal cochlear sector, while stimulation at a more apical site resulted in increased neuronal survival extending to more apical regions.

Animals↗

PubMed1991

Chronic intracochlear electrical stimulation induces selective survival of spiral ganglion neurons in neonatally deafened cats.

Ten newborn kittens were deafened by systemic administration of neomycin sulfate. Profound hearing losses were documented by ABR and FFR (500 Hz) testing. At 9-17 weeks of age, the young deafened cats were unilaterally implanted with a multichannel scala tympani electrode. Six of the animals were chronically stimulated at 6 dB above electrically evoked ABR thresholds for 1 h/day for periods of 1 month or 3 months. Stimuli were charge-balanced biphasic pulses (200 microseconds/phase, 30 pps.) The remaining 4 cats underwent identical deafening and implantation schedules but were not stimulated. Results indicate that administration of neomycin in neonatal cats induced degeneration of hair cells and spiral ganglion cell loss that was bilaterally symmetrical between the two cochleas of each individual animal, although there was variation between animals in the severity of the ototoxic drug effect. In animals receiving passive (unstimulated) implants, morphometric analysis of spiral ganglion cell density showed no significant difference in ganglion cell survival between the implanted cochleas and the contralateral control ears. In contrast, animals that were chronically stimulated for 3 months showed significantly better neuronal survival in implanted and stimulated cochleas as compared to contralateral deafened control ears. The induced conservation of spiral ganglion neurons was observed consistently within the basal cochlear region near the stimulating electrodes. In more apical regions there was no significant difference between the stimulated and control cochleas. The mechanisms underlying this selective conservation of spiral ganglion neurons induced by chronic intracochlear electrical stimulation are uncertain. Since no comparable chronic stimulation studies have been conducted in adults, it is not known whether similar conservation effects could be induced in mature animals.

Animals↗

PubMed1991

Chronic intracochlear electrical stimulation in the neonatally deafened cat. II. Temporal properties of neurons in the inferior colliculus.

The major focus of this study was to define the effects of chronic intracochlear electrical stimulation (ICES) on single unit responses in the inferior colliculus from three experimental groups: 1) normal adults 2) neonatally-deafened/unstimulated adults; and 3) neonatally-deafened/chronically stimulated adults. The major findings include: 1) IC neurons in normal adults showed a diversity of perstimulus responses to ICES which were qualitatively similar to those evoked by acoustic stimuli. They responded with: an onset burst, a sustained discharge, a decrease in their spontaneous activity, or a strong post-stimulus response. The excitatory responses showed either a monotonic or a nonmonotonic increase in activity with increasing stimulus intensity. Response latencies ranged from 5 to over 40 ms. 2) Responses to ICES in normal and deafened/unstimulated animals were virtually indistinguishable from one another. 3) In contrast, responses to ICES in neonatally deafened stimulated animals were different from normal and from deafened, unstimulated animals. Their perstimulus response latencies were significantly shorter, their late response latencies were significantly longer, and the frequency of occurrence of inhibitory and late responses were significantly higher. From these results we conclude that the responses to intracochlear electrical stimulation are directly comparable to those observed following normal acoustic stimulation; that development of cochleotopic organization of the inferior colliculus is not affected by the almost complete lack of normal acoustic input experienced by neonatally deafened animals; and that the basic response properties of IC units are likewise unaffected by neonatal deafening. Moreover, the results suggest that, although the limited regime of electrical stimulation employed in these studies produced no major qualitative distortions in the perstimulus response patterns of IC neurons, it did result in some quantitative changes in those responses.

Animals↗