Biomedical subjects

J F Willott

Publications and source records attributed to J F Willott.

At least 37 records · Page 2Linked to original sources

PubMed1996

Physiological plasticity in the auditory system and its possible relevance to hearing aid use, deprivation effects, and acclimatization.

Alterations in the physiological and/or the anatomical properties of the central auditory system (neural plasticity) can be induced by unilateral or bilateral sensorineural hearing loss, auditory stimulation, and conditioning in which sounds are used as conditioned stimuli. These types of neural plasticity have implications for hearing aid use, acclimatization, and deprivation effects. The occurrence of hearing-loss-induced plasticity suggests that the organization of the central auditory system may be altered by the time a hearing aid is fitted. The success of hearing aids may depend, therefore, on how the auditory system responds to the reintroduction of certain sounds by amplification. For example, enhanced auditory stimulation provided by hearing aids may induce "secondary" plasticity in the auditory system, which might contribute to acclimatization and/or deprivation effects. Such functional changes might be further modulated by reinforcing responses to reintroduced sounds using conditioning techniques. This article reviews relevant literature on auditory system plasticity--drawn largely from animal research--with the goal of providing insight into possible mechanisms of acclimatization and deprivation effects.

Brain↗

PubMed1996

Report of the Eriksholm Workshop on auditory deprivation and acclimatization.

The terminology used in studies documenting changes in auditory performance following fitting of hearing aids has been diverse. Definitions for the auditory deprivation effect and auditory acclimatization are offered as a first step in rationalization. Two statements summarize current knowledge concerning auditory deprivation effects and auditory acclimatization, as well as considering the potential implications for research, field trial and clinical practice applications. Potential areas for future research are identified.

Auditory Perception↗

PubMed1996

Anatomic and physiologic aging: a behavioral neuroscience perspective.

Because hearing is accomplished by the brain (with neural input from the cochlea), presbyacusis can be ultimately accounted for by changes in brain activity that accompany aging. The anatomic and physiologic changes that accompany aging are of two basic types: the central effects of biological aging (CEBA) and the central effects of peripheral pathology (CEPP). Research using inbred mice and other animal models has provided insights into both CEPP and CEBA, and some implications of this research are reviewed, including the following. Age-related cochlear pathology results in changes in how frequency is "mapped" in the central auditory system (CAS), especially at higher anatomic levels, and this has potentially negative consequences for hearing. Aging and/or age-related hearing loss may impair neural inhibition in the CAS. CEPP may result in abnormalities in neural responses involved in binaural hearing and cause exaggerated "masking" of neural responses by noise. The extent of age-related anatomic change (CEBA and CEPP) varies among CAS subdivisions and accelerates during the terminal phase of life. Genes have been found to influence the time course and severity of presbyacusis as well as the role dietary restriction plays in ameliorating age-related hearing loss in mice.

Age Factors↗

PubMed1995

Genetics of age-related hearing loss in mice. II. Strain differences and effects of caloric restriction on cochlear pathology and evoked response thresholds.

The effects of genotype and diet on age-related hearing loss were evaluated using auditory brainstem response (ABR) thresholds and post-mortem cochlear histopathology in 5 inbred mouse strains, CBA/H-T6J (CH), DBA/2J (D2), C57BL/6J (B6), BALB/cByJ (BY) and WB/ReJ (WB), and their 10 F1 hybrid strains. The mice had been maintained since weaning on either a high-energy (HE) control diet or low-energy (LE) calorically restricted diet. ABR thresholds were obtained when the mice were 23 months old; the mice were allowed to age until they died from natural causes prior to obtaining the histological material. The severity of post-mortem cochlear pathology in mice maintained with the HE diet supports our earlier genetic model which postulated that B6, BY, and WB strains each possessed a different recessive allele causing age-related hearing loss, D2 mice possessed all 3 genes, and CH mice possessed none. The histopathology indicates that the genes act at the cochlear level. Dietary restriction resulted in increased longevity in a number of strains, but age-related changes in cochlear pathology were not ameliorated in any of these; indeed, in some strains long-lived LE mice exhibited severe cochlear degeneration. In strains for which longevity was not extended by caloric restriction, only B6 mice exhibited an ameliorative effect of the LE diet on cochlear pathology. ABRs in 23-month-olds indicated a slowing of age-related hearing loss in LE mice of 3 F1 hybrid strains.

Analysis of Variance↗

PubMed1995

Modification of the acoustic startle response in hearing-impaired C57BL/6J mice: prepulse augmentation and prolongation of prepulse inhibition.

Modification of acoustic startle amplitude by a 10-ms tone prepulse (S1) was evaluated as a function of the interstimulus interval (ISI) between the onset of S1 and the onset of the startle-evoking stimulus (S2). Subjects were normal-hearing 1-month-old C57BL/6J (C57) mice and CBA/CaJ mice and 5-month-old C57 mice with high-frequency hearing loss. With a 2-ms ISI, 5-month-old C57 mice (but not the normal-hearing mice) exhibited pronounced prepulse augmentation (PPA) of startle: Amplitudes were much larger when S1 was present. Prepulse inhibition (PPI) occurred with ISIs of 10-100 ms in all subject groups. With long ISIs of 200 and 500 ms, however, PPI was strong only in 5-month-old C57 mice and only with S1 frequencies of 8, 12, and 16 kHz. Physiological studies of neural plasticity have shown that frequencies of 8-16 kHz become "over-represented" (more neurons responding) in the central auditory system of C57 mice, suggesting a link with prolonged PPI observed here.

Animals↗

PubMed1994

Responses of inferior colliculus neurons in C57BL/6J mice with and without sensorineural hearing loss: effects of changing the azimuthal location of an unmasked pure-tone stimulus.

Azimuth functions (discharge rates evoked by tone bursts as a function of stimulus azimuth) were obtained from neurons in the inferior colliculus (IC) of C57 mice aged 2, 7 and 12 months. Because of a gene that affects the cochlea, C57 mice exhibit high-frequency sensorineural hearing loss at 7 and 12 months. Azimuth functions were examined for differences that might be related to the decline in localization acuity that accompanies hearing loss in this strain. Irrespective of age group, nearly all neurons in the central area of the IC were sensitive to the azimuth of a best frequency (BF) stimulus, as revealed by azimuth functions in which firing rates varied by more than 50% from maximum to minimum at one or more intensities. The age groups were similar in many respects (e.g., there were no significant differences in the proportion of functions meeting the criterion for direction sensitivity, the proportion of neurons with direction sensitive functions over a range of intensities, azimuth function shapes, the locations or stability of 'borders' separating angles evoking high versus low discharge rates). However, in 7- and 12-month-olds: the proportion of IC neurons in which the strongest excitatory driving was evoked by ipsilateral stimulation was significantly larger; azimuth function borders were more likely to be 'reversed' (i.e., the high rates being evoked by the more ipsilateral angle); and a greater proportion of azimuth functions met the criterion for direction sensitivity only minimally. The findings suggest that binaural excitatory-inhibitory interactions are altered in IC neurons of hearing-impaired mice.

Acoustic Stimulation↗

PubMed1994

Responses of inferior colliculus neurons in C57BL/6J mice with and without sensorineural hearing loss: effects of changing the azimuthal location of a continuous noise masker on responses to contralateral tones.

Extracellular recordings were obtained from inferior colliculus neurons of young adult (2-month-old) C57 mice with normal hearing and middle-aged (6-month-old) C57 mice with sensorineural hearing loss as they responded to best frequency (BF) tones (signal) in the presence of a continuous background noise (masker). Rate/level functions were obtained for the signal alone, noise bursts alone, and the signal in continuous noise as a function of masker location. For both groups of mice, thresholds for BF tones were significantly elevated in the presence of noise at all three noise locations. Separating the signal and masker sources significantly improved masked tone thresholds of 2-month-old mice but not hearing-impaired mice. The decreased ability of middle-aged mice to benefit from separation of the signal and masker sources may reflect alterations in binaural processing as a result of sensorineural hearing loss.

Acoustic Stimulation↗

PubMed1994

Morphology of the cochlear nucleus in CBA/J mice with chronic, severe sensorineural cochlear pathology induced during adulthood.

The effects of chronic cochlear impairment on morphological features of the adult cochlear nucleus (CN) were assessed in CBA/J mice in which severe sensorineural damage had been induced by exposure to intense noise. Sections from various CN subdivisions, stained for Nissl substance and fibers, were quantitatively evaluated in four groups of noise-exposed mice that differed with regard to the age at noise exposure (2, 6, or 11 months), age at the time the CN was evaluated (6, 11, or 24 months), and the duration (chronicity) of sensorineural impairment (4, 5, 13, or 18 months). Like-aged, non-exposed CBA mice were used as controls, so the effects of peripheral damage and aging could be compared. Cochlear damage produced significant changes in CN subdivisions thought to receive the heaviest input from cochlear afferents (anteroventral CN, octopus cell area, dorsal CN layer III). These changes included a reduction of neuropil volume, reductions in neuron size, and increases in neuronal packing density that were complementary to reduced volume in these subdivisions. Effects on neuron number were minimal in all subdivisions. Central changes in noise-exposed mice were absent or diminished in DCN layers I and II, which receive relatively less input from primary fibers. The age at onset and chronicity of damage had little to do with the severity of central effects of cochlear damage. The effects of cochlear damage were not additive with age-related changes seen in the old controls.

Age Factors↗

PubMed1994

Prepulse inhibition of the startle response in mice: relationship to hearing loss and auditory system plasticity.

Prepulse inhibition was used with C57BL/6J (C57) mice to assess behavioral-perceptual correlates of previously demonstrated physiological changes in the central auditory system associated with age-related hearing loss. Normal-hearing CBA/CaJ (CBA) mice and DBA/2J (DBA) mice, which exhibit extremely rapid hearing loss, were also tested. Tone prepulse stimuli (S1s) were presented 100 ms prior to a startle-evoking noise stimulus (S2), and a decrease in startle amplitude served as the measure of startle modification. As high-frequency hearing declined in C57 mice between 1 and 12 months of age, the efficacy of lower-frequency S1s was significantly enhanced. CBA mice exhibited no age-related changes in startle modification. DBA mice exhibited changes similar to those observed in C57s but at an accelerated rate. The enhanced behavioral saliency of low and middle frequencies in C57 and DBA mice appears to be a consequence of neural plasticity in the central auditory system.

Animals↗

PubMed1993

Plasticity of auditory cortex associated with sensorineural hearing loss in adult C57BL/6J mice.

The representation of frequency was mapped in the primary auditory cortex (AI) of C57BL/6J (C57) mice during young adulthood (1.5-2 months) when hearing is optimal, and at 3, 6, and 12 months of age, a period during which progressive, high frequency, sensorineural hearing loss occurs in this strain. Maps were also obtained from CBA/CaJ mice which retain good hearing as they age. In AI of young adult C57 mice and CBA mice, characteristic frequencies (CFs) of multiple-unit clusters were easily identified with extracellular recordings, and a general tonotopic organization was observed from dorsal (high frequency) to ventral and caudal (low frequency). In individual cases there appeared to be deviations from the above tonotopic organization, despite the fact that inbred mice are genetically invariant. As progressive loss of high frequency sensitivity ensued peripherally, a substantially increased representation of middle frequencies was observed in AI. There was no apparent change in the surface area of the auditory cortex despite the elimination of high frequencies, and virtually the entire auditory cortex became devoted to the middle frequencies (especially 10-13 kHz) for which sensitivity remained high. Similar age-related changes were not observed in normal-hearing CBA mice. These findings indicate that plasticity in the representation of frequency in AI is associated with high frequency hearing loss in C57 mice.

Acoustic Stimulation↗

PubMed1993

Effects of bilateral lesions of auditory cortex in mice on the acoustic startle response.

The acoustic startle response (ASR) was used to investigate the effects of auditory cortical lesions on a brain stem-mediated auditory behavior. The ASRs were obtained longitudinally from young adult C57BL/6J mice before bilateral ablation of auditory cortex, 1 day after ablation, and 1 month later. Control mice received lesions of nonauditory cortex. For some mice, averaged brain stem-evoked responses (ABR) were obtained, and these indicated no effects of lesions on auditory sensitivity. One month after surgery, mice with auditory cortex ablations were statistically indistinguishable from controls on all suprathreshold measures of ASR. However, 1 day after ablation of auditory cortex, experimental animals (but not controls) exhibited a change in ASR amplitude (but not threshold or latency). When a noise burst of 80 dB SPL was used to elicit the ASR, the amplitude was diminished, but with a 110 dB stimulus, amplitude was enhanced. The findings can be interpreted in one of two ways: temporary interference with modulation of the ASR normally performed by auditory cortex; or a general effect of auditory cortex ablation on brain stem auditory circuits not specific to the ASR. In any event, if auditory cortex plays a modulatory role with regard to the ASR, it is apparently nonessential and/or readily compensated for after ablation.

Acoustic Stimulation↗

PubMed1993

Genetics of age-related hearing loss in mice: I. Inbred and F1 hybrid strains.

The auditory-evoked brainstem response (ABR) was used to assess hearing loss in five inbred strains of mice and all ten combinations of F1 hybrids. The inbred strains are CBA/H-T6J (CH), DBA/2J (D2), C57BL/6J (B6), BALB/cByJ (BY) and WB/ReJ (WB). The F1 hybrids are CHD2, CHB6, CHBY, CHWB, D2B6, D2BY, D2WB, B6BY, B6WB, and BYWB. At middle age (12, 16 months), mice were tested with click stimuli. At a relatively old age (23 months, near inbreds' median life span), they were tested with both click and tone-pip stimuli. The CH mice and their four F1 hybrid strains exhibit lower thresholds than the other strains, with the F1 strains being most sensitive (i.e., hybrid vigor). The D2 inbred and the three D2 F1 hybrids (excluding CHD2) exhibit the earliest and most severe hearing losses. The B6, BY and WB inbred strains exhibit severe hearing losses between 16 and 23 months of age; however, the B6BY, B6WB and BYWB F1 hybrids have significantly lower thresholds than their parental strains (genetic complementation). These data support a genetic model for recessive alleles at three different loci which contribute to age-related hearing loss. The CH mice have none of the recessive alleles, and the D2 mice are homozygous recessive for all three; the B6, BY and WB inbred strains are homozygous recessive respectively for one of the three loci.

Acoustic Stimulation↗

PubMed1992

Morphology of the dorsal cochlear nucleus in C57BL/6J and CBA/J mice across the life span.

The morphology of the dorsal cochlear nucleus (DCN) was evaluated across the life span in inbred C57BL/6J (C57) and CBA/J (CBA) mice using 5 age groups (young adult to very old). C57 mice exhibit progressive cochlear sensorineural pathology and hearing loss during middle age; CBA mice have only modest sensorineural pathology late in life. DCN layers I, II, and III were evaluated histologically with serial sections stained for Nissl and fibers. DCN volume decreased with age in C57 mice, but the change began earliest and was most pronounced in layer III. In CBA mice, volume increased during the first year of life and decreased only in the oldest mice. All major DCN cell types were found in both strains at all ages. There was an age-related decrease in the mean size of neurons in C57 mice that was first observed in layer III. In CBA mice, only a nonsignificant trend toward smaller neurons was observed in the oldest mice. An age-related decline in the number of neurons in layer III (but not in layers I and II) occurred in C57 mice. Aged CBA mice exhibited no significant loss of DCN neurons. Thus, age-related changes in the DCN were much more pronounced in C57 mice than in CBA mice, and the changes in C57 mice were most pronounced in layer III. Because layer III receives most of the DCN's primary auditory input, it would be directly affected by age-related hearing loss and degeneration of spiral ganglion cells in C57 mice. This suggests that the age-related changes observed in DCN layer III of C57 mice are affected by progressive peripheral degenerative changes; when peripheral loss is minimal (CBA mice), less substantial age-related changes are observed.

Aging↗

PubMed1991

Comparison of the auditory sensitivity of neurons in the cochlear nucleus and inferior colliculus of young and aging C57BL/6J and CBA/J mice.

Thresholds of neurons to sounds were compared as a function of central auditory structure [ventral cochlear nucleus (VCN), dorsal cochlear nucleus (DCN), and inferior colliculus (IC)] in young and middle-aged C57BL/6J mice (multiple- and single-unit recordings) and in young and old CBA/J mice (single-unit recordings). Middle-aged C57 mice show progressive loss of sensitivity to high frequencies and noise due to cochlear pathology; CBA mice show little loss of sensitivity through most of their lifespan. Multiple-unit threshold curves (MTCs) for tones indicated that neurons in the C57 VCN suffered a greater degree of age-related loss of sensitivity than neurons in the IC (from an earlier study). Furthermore, whereas the low frequency portions of MTCs in IC neurons in high frequency tonotopic regions typically become 'sensitized' in middle-aged C57 mice (i.e., lower thresholds than young mice), such was not the case for VCN neurons. In contrast to VCN neurons, MTCs of the population of DCN neurons studied were statistically indistinguishable from those of the IC. Measurements of single-unit response areas in C57 mice corroborated the MTCs. In CBA mice, little effect of age was found in comparing single-unit response areas of young and old mice. The findings indicate that sensorineural impairment in middle-aged C57 mice is accompanied by threshold changes that are more severe in the VCN than in the IC or DCN. Because the VCN and DCN are believed to play different roles in hearing, the functions they support should, likewise, be affected to different extents by age-related hearing loss.

Acoustic Stimulation↗

PubMed1990

Morphology of the octopus cell area of the cochlear nucleus in young and aging C57BL/6J and CBA/J mice.

The influence of aging and age-related cochlear impairment on the ventral cochlear nucleus was evaluated by measuring morphological properties of the octopus cell area (OCA) in five age groups of inbred C57BL/6J and CBA/J mice (young adult to very old). The former strain demonstrates progressive cochlear sensorineural pathology and hearing loss during middle age; the latter has only modest sensorineural pathology late in life. Histological sections of the OCA were evaluated with serial sections and several strains for neurons, glia, and fibers, and Golgi impregnations were also used. Aging was associated with a decrease in volume of the OCA, a loss of neurons, slight decrease in neuron size, increased packing density of glial cells, and changes in dendrites ranging from minor to total loss of primary branches. The greatest changes occurred in extreme old age, beyond the median lifespan. Age-related changes were not exacerbated by sensorineural pathology in aging C57BL/6J mice. Individual octopus cells varied greatly in the extent of age-related abnormality.

Aging↗

PubMed1990

Effects of inferior colliculus lesions on the acoustic startle response.

"Nonspecific" electrolytic lesions (with respect to subdivision) of the mouse inferior colliculus (IC) resulted in the attenuation of acoustic startle response (ASR) amplitudes on the 1st post-operative day, but ASR amplitudes increased to above baseline levels 1 week later. Lesions of the IC central nucleus (CN) also attenuated ASR amplitudes on the 1st postsurgery day, but startle amplitudes recovered to baseline levels 1 week after surgery. Lesions of the IC lateral nucleus (LN) or dorsal cortex (DC) resulted in elevation of startle amplitudes above baseline 7 days after surgery and produced enhanced ASR amplitudes to repeated stimuli. Fourteen days after the surgery, lesion effects on startle amplitudes remained the same as those on Day 7 for each lesion condition. The present findings implicate the ICLN and the ICDC as inhibitory modulators of the ASR, but indicate only a minor role for the ICCN.

Animals↗

PubMed1990

Central physiological correlates of ageing and presbycusis in mice.

Responses of neurons in the central auditory system of ageing mice suggest several sources of age-related problems in hearing. The central representation of frequency (tonotopic organization) is disrupted in mice with presbycusis, implying a cause of problems with frequency coding. In very old mice with only minimal hearing loss, normal-responding neurons co-exist with "sluggish" neurons, which suggests there is a process of attrition that affects some neurons more than others. Spontaneous activity increases in neurons of older mice, implying a decrease in the physiological signal-to-noise ratio. The effects of age-related hearing loss are more severe in the ventral cochlear nucleus than in the dorsal cochlear nucleus, suggesting that various functional circuits may be more or less vulnerable to presbycusis.

Acoustic Stimulation↗

PubMed1988

Aging and presbycusis: effects on 2-deoxy-D-glucose uptake in the mouse auditory brain stem in quiet.

Autoradiography was used to assess the incorporation of [2-14C]deoxy-D-glucose by the auditory brain stem of young and aging mice of the C57BL/6 strain (which demonstrates progressive chronic sensorineural hearing loss) and the CBA strain (which maintains good hearing until late in life). Animals were injected with labeled 2-deoxyglucose and placed in quiet for 45 min; brain stem sections were prepared for autoradiography. The amounts of 2-deoxyglucose incorporated into the anterior ventral cochlear nucleus (AVCN), inferior colliculus (IC), and trigeminal nerve (TN) were densitometrically analyzed. Within each subject, the densities of the three structures were statistically compared. In every mouse, inferior colliculus density was greater than that of the anterior ventral cochlear nucleus, which was greater than trigeminal nerve density. To compare subject groups, relative densities (inferior colliculus and anterior ventral cochlear nucleus re: trigeminal nerve) were used; no significant differences were found between groups. Thus, aging, with or without severe loss of hearing, is not associated with altered incorporation of 2-deoxyglucose (and presumably glucose) in quiet.

Aging↗