Impact of sound exposure and aging on brain-derived neurotrophic factor and tyrosine kinase B receptors levels in dorsal cochlear nucleus 80 days following sound exposure.

Recent studies suggested that acute sound exposure resulting in a temporary threshold shift in young adult animals within a series of maladaptive plasticity changes in central auditory structures. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is involved in post-trauma peripheral hair cell and spiral ganglion cell survival and has been shown to modulate synaptic strength in cochlear nucleus following sound exposure. The present study evaluated levels of BDNF and its receptor (tyrosine kinase B, [TrkB]) in the dorsal cochlear nucleus (DCN) following a unilateral moderate sound exposure in young (7-8 months) and aged (28-29 months) Fischer Brown Norway (FBN) rats. Eighty days post-exposure, auditory brainstem response (ABR) thresholds for young exposed rats approached control values while aged exposed rats showed residual permanent threshold shifts (PTS) relative to aged controls. BDNF protein levels were significantly up-regulated by 9% in young exposed fusiform cells ipsilateral to the exposure. BDNF levels in aged sound-exposed fusiform cells increased 31% ipsilateral to the exposure. Protein levels of the BDNF receptor, TrkB, were also significantly increased in aged but not in young sound-exposed DCN fusiform cells. The present findings suggest a relationship between the up-regulation of BDNF/TrkB and the increase in spontaneous and driven activity previously observed for aged and sound-exposed fusiform cells. This might be due to a selective maladaptive compensatory down-regulation of glycinergic inhibition in DCN fusiform cells.

Plasticity at glycinergic synapses in dorsal cochlear nucleus of rats with behavioral evidence of tinnitus.

Fifteen percent to 35% of the United States population experiences tinnitus, a subjective "ringing in the ears". Up to 10% of those afflicted report severe and disabling symptoms. Tinnitus was induced in rats using unilateral, 1 h, 17 kHz-centered octave-band noise (116 dB SPL) and assessed using a gap-startle method. The dorsal cochlear nucleus (DCN) is thought to undergo plastic changes suggestive of altered inhibitory function during tinnitus development. Exposed rats showed near pre-exposure auditory brainstem response (ABR) thresholds for clicks and all tested frequencies 16 weeks post-exposure. Sound-exposed rats showed significantly worse gap detection at 24 and 32 kHz 16 weeks following sound exposure, suggesting the development of chronic, high frequency tinnitus. Message and protein levels of alpha(1-3,) and beta glycine receptor subunits (GlyRs), and the anchoring protein, gephyrin, were measured in DCN fusiform cells 4 months following sound exposure. Rats with evidence of tinnitus showed significant GlyR alpha(1) protein decreases in the middle and high frequency regions of the DCN while alpha(1) message levels were paradoxically increased. Gephyrin levels showed significant tinnitus-related increases in sound-exposed rats suggesting intracellular receptor trafficking changes following sound exposure. Consistent with decreased alpha(1) subunit protein levels, strychnine binding studies showed significant tinnitus-related decreases in the number of GlyR binding sites, supporting tinnitus-related changes in the number and/or composition of GlyRs. Collectively, these findings suggest the development of tinnitus is likely associated with functional GlyR changes in DCN fusiform cells consistent with previously described behavioral and neurophysiologic changes. Tinnitus related GlyR changes could provide a unique receptor target for tinnitus pharmacotherapy or blockade of tinnitus initiation.

Age-related changes in glycine receptor subunit composition and binding in dorsal cochlear nucleus.

Age-related hearing loss, presbycusis, can be thought of, in part, as a slow progressive peripheral deafferentation. Previous studies suggest that certain deficits seen in presbycusis may partially result from functional loss of the inhibitory neurotransmitter glycine in dorsal cochlear nucleus (DCN). The present study assessed age-related behavioral gap detection changes and neurochemical changes of postsynaptic glycine receptor (GlyRs) subunits and their anchoring protein gephyrin in fusiform cells of young (7-11 months) and aged (28-33 months) Fischer brown Norway (FBN) rats. Aged rats showed significantly (20-30 dB) elevated auditory brainstem-evoked response thresholds across all tested frequencies and worse gap detection ability compared to young FBN rats. In situ hybridization and quantitative immunocytochemistry were used to measure GlyR subunit message and protein levels. There were significant age-related increases in the alpha(1) subunit message with significant age-related decreases in alpha(1) subunit protein. Gephyrin message and protein showed significant increases in aged DCN fusiform cells. The pharmacologic consequences of these age-related subunit changes were assessed using [3H] strychnine binding. In support of the age-related decrease of alpha(1) subunit protein levels in DCN, there was a significant age-related decrease in the total number of GlyR binding sites with no significant change in affinity. These age-related changes may reflect an effort to reestablish a homeostatic balance between excitation and inhibition impacting on DCN fusiform cells by downregulation of inhibitory function in the face of an age-related loss of peripheral input. Age-related decrease in presynaptic glycine release results in altered subunit composition and this may correlate with loss of temporal coding of the aged fusiform cell in DCN. The previously reported role for gephyrin in retrograde intracellular receptor subunit trafficking could contribute to the alpha(1) decrease in the face of increased message.

Aged-related loss of temporal processing: altered responses to amplitude modulated tones in rat dorsal cochlear nucleus.

Loss of temporal processing is characteristic of age-related loss of speech understanding observed in the elderly. Inhibitory glycinergic circuits provide input onto dorsal cochlear nucleus (DCN) projection neurons which likely serve to modulate excitatory responses to time-varying complex acoustic signals. The present study sought to test the hypothesis that age-related loss of inhibition would compromise the ability of output neurons to encode sinusoidally amplitude modulated (SAM) tones. Extracellular recordings were obtained from young and aged FBN rat DCN putative fusiform cells. Stimuli were SAM tones at three modulation depths (100, 50, and 20%) at 30 dB hearing level with the carrier frequency set to the unit's characteristic frequency. Discharge rate and synchrony were calculated to describe SAM responses. There were significant age-related changes in the shape and peak vector strength [best modulation frequency (BMF)] of temporal modulation transfer functions (tMTFs), with no significant age-related changes in rate modulation transfer functions (rMTFs) at BMF. Young neurons exhibited band-pass tMTFs for most SAM conditions while aged fusiform cells exhibited significantly more low-pass or double-peaked tMTFs. There were significant differences in tMTFs between buildup, pauser-buildup, and wide-chopper temporal response types. Young and aged wide-choppers displayed significantly lower vector strength values than the other two temporal DCN response types. Age-related decreases in the number of pauser-buildup response types and increases in wide-chopper types reported previously, could account, in part, for the observed loss of temporal coding of the aged fusiform cell. Age-related changes in SAM coding were similar to changes observed with receptor blockade of glycinergic inhibition onto fusiform cells and consistent with previously observed age-related loss of endogenous glycine levels and changes in normal adult glycine receptor function. DCN changes in SAM coding could, in part, underpin temporal processing deficits observed in the elderly.

Dorsal cochlear nucleus responses to somatosensory stimulation are enhanced after noise-induced hearing loss.

Multisensory neurons in the dorsal cochlear nucleus (DCN) achieve their bimodal response properties [Shore (2005) Eur. J. Neurosci., 21, 3334-3348] by integrating auditory input via VIIIth nerve fibers with somatosensory input via the axons of cochlear nucleus granule cells [Shore et al. (2000) J. Comp. Neurol., 419, 271-285; Zhou & Shore (2004)J. Neurosci. Res., 78, 901-907]. A unique feature of multisensory neurons is their propensity for receiving cross-modal compensation following sensory deprivation. Thus, we investigated the possibility that reduction of VIIIth nerve input to the cochlear nucleus results in trigeminal system compensation for the loss of auditory inputs. Responses of DCN neurons to trigeminal and bimodal (trigeminal plus acoustic) stimulation were compared in normal and noise-damaged guinea pigs. The guinea pigs with noise-induced hearing loss had significantly lower thresholds, shorter latencies and durations, and increased amplitudes of response to trigeminal stimulation than normal animals. Noise-damaged animals also showed a greater proportion of inhibitory and a smaller proportion of excitatory responses compared with normal. The number of cells exhibiting bimodal integration, as well as the degree of integration, was enhanced after noise damage. In accordance with the greater proportion of inhibitory responses, bimodal integration was entirely suppressive in the noise-damaged animals with no indication of the bimodal enhancement observed in a sub-set of normal DCN neurons. These results suggest that projections from the trigeminal system to the cochlear nucleus are increased and/or redistributed after hearing loss. Furthermore, the finding that only neurons activated by trigeminal stimulation showed increased spontaneous rates after cochlear damage suggests that somatosensory neurons may play a role in the pathogenesis of tinnitus.

Age-related loss of the GABA synthetic enzyme glutamic acid decarboxylase in rat primary auditory cortex.

Age-related changes within the auditory brainstem typically include alterations in inhibitory neurotransmission and coding mediated by GABA and glycinergic circuits. As part of an effort to evaluate the impact of aging on neurotransmission in the higher auditory centers, the present study examined age-related changes in the GABA synthetic enzyme, glutamic acid decarboxylase (GAD), in rat primary auditory cortex (AI), which contains a vast network of intrinsic and extrinsic GABAergic circuits throughout its layers. Message levels of the two GAD isoforms found in brain, GAD(65) and GAD(67), and GAD(67) protein levels were compared in young adult, middle-aged and aged rats using in situ hybridization and quantitative immunocytochemistry, respectively. For comparison, age-related GAD changes were also assessed in the parietal cortex and hippocampus. Significant age-related decreases in GAD(65&67) messages were observed in AI layers II-VI of aged rats relative to their young adult cohorts. The largest changes were identified in layer II (GAD(65): -26.6% and GAD(67): -40.1%). GAD(67) protein expression decreased significantly in parallel with mRNA decreases in all layers of AI. Adjacent regions of parietal cortex showed no significant GAD(67) protein changes among the age groups, except in layer IV. As previously described, GAD(67) message and protein levels in selected hippocampal regions were significantly reduced in aged rats. Age-related GAD reductions likely reflect decreases in both metabolic and pre-synaptic GABA levels suggesting a plastic down-regulation of normal adult inhibitory GABA neurotransmission. Consistent with the present findings, functional studies in primate visual cortex and preliminary studies in AI find coding changes suggestive of altered inhibitory processing in aged animals. An age-related loss of normal adult GABA neurotransmission in AI would likely alter temporal coding properties and could contribute to the loss in speech understanding observed in the elderly.

Effects of hormone replacement therapy on olfactory sensitivity: cross-sectional and longitudinal studies.

OBJECTIVE: To determine whether hormone replacement therapy (HRT) preserved or improved olfactory sensitivity in healthy postmenopausal women. METHODS: Sixty-two postmenopausal women participated in a cross-sectional study of olfactory sensitivity involving detection, intensity discrimination, quality discrimination and two measures of quality recognition. In addition, 24 postmenopausal women participated in a longitudinal study of olfactory sensitivity. This study allowed for the measurement of estrogen effects (while holding practice effects constant) and the measurement of practice effects (while holding HRT conditions constant). RESULTS: In the cross-sectional study, we were unable to detect any differences between those receiving HRT and those not receiving HRT. Duration of exposure to HRT was examined by selecting women who had 5 or more years of exposure to their HRT regimen. Even after the data were reorganized into those for opposed- and unopposed-estrogen use, we were unable to detect any differences. However, olfactory threshold increased as a function of increasing age, regardless of HRT status. A gradual decrease in ability to detect odors was observed from the 4th to the 6th decade, with a greater decrease between the 6th and 7th decades. In the longitudinal study, no effects of HRT were detected even when practice effects were uncontrolled. Practice effects were assessed both between and within subjects. No effects of practice were detected when initial baseline performance was used as a covariate. CONCLUSION: Although prophylactic HRT has been suggested to be associated with improved olfactory function, we find that its use in healthy postmenopausal women does not enhance performance in a wide range of olfactory tasks.

Anticipation in a unique family with Charcot-Marie-Tooth syndrome and deafness: delineation of the clinical features and review of the literature.

Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of polyneuropathies characterized by degeneration of peripheral nerves, resulting in distal muscle atrophy, sensory loss, and deformities of hands and feet. We have studied 34 individuals in a large 84-member four-generation central Illinois family with autosomal dominant Charcot-Marie-Tooth and deafness. Nerve conduction velocities are consistent with type 1 CMT. Audiological evaluation revealed both auditory neuropathy and cochlear involvement in affected individuals. There is increasing clinical severity and younger age of onset of CMT and deafness with each progressive generation, suggestive of anticipation (P < 0.05). The proband, a female diagnosed at birth with hypotonia, bilateral vocal cord palsy, swallowing incoordination, and hearing impairment, died at age 18 months. Another individual died at the age of 3 months from hypotonia later attributed to CMT. Genetic analysis indicated that affected individuals in this family do not have the common 1.4 Mb duplication associated with type 1A CMT; however, all affected individuals have a unique G to C transversion at position 248 in coding exon 3 of the peripheral myelin PMP22 gene located on chromosome 17p11.2-p12. This mutation is predicted to cause an Ala67Pro substitution in the second transmembrane domain of PMP22, consistent with the molecular cause of the CMT phenotype. However, it does not explain the cochlear component of the deafness, the clinical observation of anticipation, and other features in this family.

Predicting fall risks in an elderly population: computer dynamic posturography versus electronystagmography test results.

OBJECTIVES/HYPOTHESIS: Falls are the leading cause of morbidity and mortality for persons aged 65 years and older, with more than 2 million people falling and sustaining serious injury annually. This study compared computer dynamic posturography (CDP) and electronystagmography (ENG) results as predictors of falls. STUDY DESIGN: Retrospective. METHODS: Thirty-three patients over the age of 65 years who presented to a balance disorders and falls prevention clinic were used for this study (22 women and 11 men, with an average age of 78.0 y and a mean fall rate of 3.5 times). All had experienced at least one fall in the year before visiting the clinic and were tested with both CDP and ENG. The CDP results were divided into subcategories (sensory organization testing and limits of stability); ENG results were divided into four categories (ocular motor, rotational chair, positional, and caloric studies). RESULTS: Test findings were classified as normal or abnormal based on age-matched normative data. Of the patients in the study, 27.3% were normal for one type of testing and abnormal for the other. Twenty-six patients (78.8%) had abnormal results on CDP, and 20 individuals (60.6%) showed ENG abnormalities (42.4% for ocular motor, 28.6% for positional, 13.6% for caloric, and 11.2% for rotational chair studies). The limits of stability category was significant in predicting multiple falls. CONCLUSION: For this population, CDP was determined to be a more sensitive test for identifying patients who have fallen, with limits of stability testing the most significant part of the CDP battery; for ENG studies, the best falls indicator was the ocular motor battery.

Pentagon copying is more impaired in dementia with Lewy bodies than in Alzheimer's disease.

OBJECTIVES: In many cases the clinical differentiation of patients with dementia with Lewy bodies (DLB) from those with Alzheimer's disease (AD) has been difficult. Because many neuropsychological studies have reported greater visuospatial/constructional impairment in DLB than in AD, it was determined whether accuracy in copying the interlocking pentagons item on the mini mental state examination (MMSE) may be helpful in distinguishing patients with DLB from those with AD relatively early in the course of the dementia. METHODS: All cases of neuropathologically proved DLB and AD in the Center for Alzheimer Disease and Related Disorders brain bank were retrospectively reviewed, and the first available MMSE for each was retrieved. Only patients with MMSE scores > or = 13 were included, indicating mild to moderate dementia. The patients' copies of the interlocking pentagons were analyzed and graded as acceptable or unacceptable according to the original instructions for grading the MMSE. RESULTS: Seventeen patients with DLB and 27 patients with AD were identified for whom MMSE with copies of the interlocking pentagons were available. Two patients with DLB (MMSEs 22 and 27) drew the pentagons acceptably, by contrast with 16 of the patients with AD (MMSEs 13-28). An unacceptable copy was associated with DLB with a sensitivity of 88% and a specificity of 59% (p = 0.002). CONCLUSIONS: For patients with MMSE scores > or = 13, an inability to accurately copy the pentagons suggests that the diagnosis is more likely DLB than AD. The results confirm the work of others on visuospatial/constructional impairment in DLB and indicate that this feature may be helpful in its diagnosis.

Age-related changes in levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2 in the rat inferior colliculus: implications for neural senescence.

Brain-derived neurotrophic factor and fibroblast growth factor 2, and their respective binding sites, tyrosine kinase B receptor and fibroblast growth factor receptor 2, are known to regulate neurite outgrowth and antioxidant enzyme activity. Several studies suggest that brain-derived neurotrophic factor and fibroblast growth factor are contained in the inferior colliculus. Previous work in our laboratories revealed dendritic and synaptic losses in the inferior colliculus of aged Fischer-344 rats, along with coincident increases in lipid peroxidation possibly linked to a decrease in activity of antioxidant enzymes. In an effort to identify potential causal mechanisms underlying age-related synaptic and dendritic losses that occur in the inferior colliculus, the present study attempted to determine if inferior colliculus levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2 expression are altered with age. Immunocytochemistry was performed in the inferior colliculus, hippocampus and cerebellum of 3-month-old F344 rats to study distributions of the full-length and truncated isoforms of tyrosine kinase B receptor, and fibroblast growth factor receptor 2. The latter two brain regions served as positive controls. For all three antigens, immunolabeling was localized primarily in somata and proximal dendrites in all subdivisions of the inferior colliculus, and in the dentate gyrus and Ammon's horn of the hippocampus. In the cerebellum, the somata and dendrites of the Purkinje cells were also immunolabeled.A significant reduction in levels of the full-length form of tyrosine kinase B receptor in 18- and 25-month-old rats (respectively, approximately 20% and 30% relative to 3-month-olds) was revealed using western blot analyses. Inferior colliculus and hippocampal levels of the truncated form were modestly decreased ( approximately 7%) as well in the two older age groups. In contrast, levels of fibroblast growth factor receptor 2 in the inferior colliculus and hippocampus were elevated by approximately 35% in the two older age groups when compared to 3-month-olds. Changes in cerebellar levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2, while similar to those in the inferior colliculus and hippocampus among the age groups, did not achieve statistical significance in this study. These findings give rise to the possibility that age-related reductions in tyrosine kinase B receptor levels could be a causal factor in the degenerative changes observed in the inferior colliculus of aged animals, including mitochondrial damage and dendritic regression. The observed increases in fibroblast growth factor receptor 2 levels may be compensatory to the increased oxidative stress. The effectiveness of the fibroblast growth factor receptor 2 response is questionable given the damage that occurs in the inferior colliculus and hippocampus of aged animals. However, the deficits could worsen in the absence of an increase in fibroblast growth factor receptor 2.

D-Methionine protects against cisplatin damage to the stria vascularis.

D-Methionine (D-met) protects against cisplatin (CDDP)-induced hearing loss and outer hair cell loss (Campbell et al., 1996). However, D-met's protective effects on the stria vascularis has not been previously investigated. The purpose of this study was to examine, using semi-quantitative analysis, whether D-met also protects the stria vascularis. We removed a basal turn section of the stria vascularis from five groups of five male Wistar rats each: (1) a CDDP-treated control group receiving a 30 min i.p. infusion of 16 mg/kg CDDP, (2) a saline-injected control group receiving an equivalent volume of saline, and (3) three groups injected with either 75, 150, or 300 mg/kg D-methionine (D-met) i.p. 30 min prior to receiving the 16 mg/kg CDDP dosing. Using transmission electron microscopy and light microscopy, we analyzed strial volume (i.e. edema), marginal cell damage classification (bulging and/or compression), and relative optical density (ROD) ratios (i.e. depletion of marginal cell cytoplasmic organelles). All three levels of D-met provided complete protection against marginal cell bulging and/or compression but only partial protection against strial edema. At 300 mg/kg, D-met significantly reduced ROD ratio degradation in the spiral prominence and middle stria vascularis regions. In Reissner's membrane region, values from the D-met pretreated group were not significantly different from either the treated or untreated control groups suggesting only partial protection for that area. Protection of marginal cell cytoplasmic organelles was also noted. In summary, D-met partially or fully protects the stria vascularis from several types of CDDP-induced damage.

Detection of glutamate decarboxylase isoforms in rat inferior colliculus following acoustic exposure.

The inferior colliculus is a central auditory structure which serves as a site for the integration of ascending and descending auditory information. Changes in central auditory structures may occur with acoustic exposure, which cannot be explained by alterations in cochlear function alone. Rats were exposed to a 10-kHz tone at 100 dB SPL for 9 h. Auditory brainstem response measures showed an initial 25-30-dB threshold shift across all tested frequencies. By 30 days post-exposure, thresholds for clicks and most frequencies returned to near control levels; however, thresholds remained elevated at 10 and 20 kHz. Inner hair cell loss was confined to apical and basal ends of the cochlea, and did not exceed 20%. Inferior colliculus levels of the two isoforms of the GABA synthetic enzyme glutamate decarboxylase (65,000 and 67,000 mol. wt forms) were measured immediately post-exposure (0 h) and at two and 30 days post-exposure using quantitative immunocytochemical and western blotting techniques. Zero-hour measures revealed a significant increase in the level of glutamate decarboxylase (mol. wt 67,000) protein (118%), as well as in the optical density (35%) of immunolabeled cells. By 30 days post-exposure, inferior colliculus protein levels of both glutamate decarboxylase isoforms were significantly below unexposed controls (39% and 21% for the 65,000 and 67,000 mol. wt forms, respectively). These studies describe increased markers for GABA immediately following acoustic exposure, followed by a decline to below control levels from two to 30 days post-exposure. It remains to be determined whether noise trauma-induced changes in glutamate decarboxylase levels in the inferior colliculus reflect protective up-regulation in response to intense stimulation, followed by the establishment of new neurotransmitter equilibrium levels.

Age-related changes in GABA(A) receptor subunit composition and function in rat auditory system.

A decline in the ability to discriminate speech from noise due to age-related hearing loss (presbycusis) may reflect impaired auditory information processing within the central nervous system. Presbycusis may result, in part, from functional loss of the inhibitory neurotransmitter GABA. The present study assessed age-related changes of the GABA(A) receptor in the inferior colliculus of young-adult, middle-aged, and aged rats related to: (i) receptor subunit composition and (ii) receptor function. Western blotting was used to measure protein levels of selected GABA(A) receptor subunits in preparations obtained from the inferior colliculus of Fischer 344 and Fischer 344/Brown-Norway F1 hybrid rats. In both strains, the aged group exhibited significant increases in gamma1 subunit protein and a decrease in alpha1 subunit protein. To examine the functional consequence of this putative age-related subunit change, we measured the ability of exogenous GABA to flux/translocate chloride ions into microsac preparations derived from Fischer 344 inferior colliculus. GABA-mediated chloride influx was significantly increased in samples prepared from the inferior colliculus of aged animals. Together with previous studies, these results strongly suggest an age-related change in GABA(A) receptor composition. These changes may reflect a compensatory up-regulation of inhibitory function in the face of significant loss of presynaptic GABA release. These findings provide one example of plastic neurotransmitter receptor changes which can occur during the ageing process.

Age-related synaptic changes in the central nucleus of the inferior colliculus of Fischer-344 rats.

The central nucleus of the inferior colliculus (ICc) is a major processing center for the ascending auditory pathways. Gamma-aminobutyric acid (GABA) and excitant amino acids (EAAs) are essential for coding many auditory tasks in the IC. Recently, a number of neurochemical and immunocytochemical studies have suggested an age-related decline in GABAergic inhibition in the ICc, and possibly excitant-amino-acid-mediated excitation as well. The objective of this study was to compare quantitatively changes in the synaptic organization of the ICc among three age groups (3, 19, and 28 months) of Fischer-344 rats. Immunogold electron microscopic methods were used to determine if there were age-related changes in the density, distribution, or morphology of GABA-immunoreactive (+) and GABA-immunonegative (-) synapses in the ICc. The data suggest similar losses of excitatory and inhibitory synapses in the ICc. There were significant reductions in the densities of GABA+ and GABA- synaptic terminals (approximately 30% and approximately 24%, respectively) and synapses (approximately 33% and approximately 26%, respectively) in the ICc of 28-month-old rats relative to 3-month-olds. The numeric values, which were adjusted to consider changes in volume of the IC with age, depict similar effects, although the effect magnitude for the adjusted values was reduced by approximately 9%. For both types of synapses, the decreases did not differ significantly from each other. The reductions in synaptic numbers appeared, to be related to a similar numeric decline in dendrites, in particular those with calibers of between 0.5 and 1.5 microm. The number and distribution of synaptic terminals on the remaining dendrites of GABA- neurons appeared not to undergo major age-related changes. GABA+ neurons, on the other hand, may have evolved patterns of synaptic and dendritic change during aging in which the distribution of synaptic terminals shifts to dendrites of larger caliber. In the 19-month group, the synaptic areas were elevated in terminals apposed to dendrites with calibers of 1.5 microm or less. However, this increase in synaptic size did not persist in the aged animals. No neuronal losses were detectable among the three age groups. Thus, the decrease in GABA and EAAs identified in the IC by previous studies may be attributable to synaptic and dendritic declines, rather than cell loss.

Age-related glycine receptor subunit changes in the cochlear nucleus of Fischer-344 rats.

Previous studies have shown that levels of binding for the strychnine-sensitive glycine receptor in the cochlear nucleus (CN) of Fischer (F344) rats decrease with age. Given the major role glycine plays in normal CN function, changes in glycine-receptor activity may contribute to central presbycusis. To further evaluate the impact of age on glycine receptors, in situ hybridization was used to assess, in three age groups of F344 rats, changes in levels of gene expression for four of its subunits. When compared with the 3-month-old rats, expression of mRNAs for alpha1 and beta subunits in the anteroventral CN decreased significantly in the 18- and 27-month-old age groups, while mRNA expression for the alpha2 subunit increased. If protein expressions are similar, these subunit changes may alter the function of glycine receptors, thereby affecting binding to its ligands.

Vestibular deficits in deaf children.

Considerable knowledge has been accumulated regarding acquired and congenital deafness in children. However, despite the intimate relationship between the auditory and vestibular systems, data are limited regarding the status of the balance system in these children. Using a test population of 15 children, aged 8 to 17 years, we performed electronystagmography testing. The test battery consisted of the eye-tracking (gaze nystagmus, spontaneous nystagmus, saccade, horizontal pursuit and optokinetic) tests, positional/positioning (Dix-Hallpike and supine) tests, and rotational chair tests. With age-matched controls, five children were tested in each of the following three categories: normal hearing, hereditary deafness, and acquired deafness. The children in the hereditary deafness category were congenitally deaf and had a family history of deafness. Those subjects in the acquired deafness category had hearing loss before the age of 2 years, after meningitis. Analysis of variance demonstrated significant differences between the two deaf groups and the control subjects in the gaze nystagmus test, saccade latencies, horizontal pursuit phase, and Dix-Hallpike and supine positionally provoked nystagmus. Also, significant differences were found in rotational chair gain and phase between the deaf and normal-hearing children. The children with acquired deafness exhibited the most profound results. In addition, there were significant differences in rotational chair gain between the acquired and congenitally deaf children. No differences were noted in horizontal pursuit gains, saccade accuracies, or saccade asymmetries. These preliminary data demonstrate that the etiologic factors responsible for congenital and acquired deafness in children may indeed affect the balance system as well. These findings of possible balance disorders in conjunction with the profound hearing loss in this patient population will have prognostic implications in the future evaluation, treatment, and rehabilitation of these patients.

Case report: olfactory function in a fertile eunuch with Kallmann syndrome.

The olfactory and gonadal dysfunction in Kallmann syndrome share a common embryologic pathophysiology. To characterize further the linkage between the hypogonadotropic hypogonadism and anosmia, the authors performed a detailed evaluation of olfactory function in a patient with Kallman Syndrome having the rare variant of partial gonadotropin deficiency (fertile eunuch). The subject was seen initially at age 16 years because of delayed puberty. He received testosterone replacement therapy and subsequently completed pubertal development. As an adult, while untreated, he had subnormal levels of serum testosterone, low gonadotropins, and normal response to luteinizing hormone- releasing hormone. He also had impotence that was reversible with testosterone therapy, and a normal sperm count. Despite the mild degree of hypogonadism, olfactory function was completely absent, and the response to nasal trigeminal stimulants was markedly attenuated. Complete anosmia may therefore be associated with gonadotropin deficiency that is only partial; the presence of anosmia does not predict the need for gonadotropin therapy to attain fertility.

Diuretic and diet effect on Menière's disease evaluated by the 1985 Committee on Hearing and Equilibrium guidelines.

Fifty-four patients, diagnosed with Menière's disease and treated with diuretics and a low-salt diet, were evaluated retrospectively with the 1985 AAO/HNS Committee on Hearing and Equilibrium (CHE) guidelines for vertigo and hearing changes. The patient data base was also evaluated with other methods that helped determine the effectiveness of the 1985 AAO/HNS CHE guidelines. After 24 months of therapy, vertigo control was complete or substantial in 79% of the patients, limited or insignificant in 19%, and worse in 2% as evaluated by the CHE 1985 guidelines. Hearing improved in 35% of the patients, was unchanged in 29%, was worse in 22%, and could not be classified by CHE guidelines in 14%. Hearing was also evaluated by comparison of individual thresholds before medical therapy, and at 22 and 74 months after the start of medical therapy. We found a stabilization of low- and mid-threshold frequencies, with an average rate of hearing loss approximating 0 dB/yr with 74 months of followup. The results of this preliminary study suggest that diuretics and a low-salt diet may decrease the natural progression of sensorineural hearing loss in patients with Menière's disease. Compared with other methods of data analysis, the 1985 CHE guidelines lacked sensitivity to evaluate the hearing changes observed.

A posteriori digital filtering to reduce signal-averaging of steady-state evoked potentials.

This paper describes a signal extraction technique that involves taking the time series representation of signals, transforming them into the frequency domain, determining the chance occurrence of power at each frequency, and filtering accordingly. An inverse Fourier transform is then used to recreate the new time domain representation, which has been appropriately filtered for extraneous noise. Thus, this technique involves a posteriori digital filtering based on a statistical criterion for component inclusion. Computer simulation indicated that, at poor signal-to-noise ratios and with fewer samples, this technique is 5 to 10 times better at signal extraction than conventional signal averaging. Examples of pattern-elicited electroretinograms (PERG's) are used to illustrate the efficacy of this method.