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J F Willott

Publications and source records attributed to J F Willott.

At least 55 records · Page 3Linked to original sources

Response properties of inferior colliculus neurons in young and very old CBA/J mice.

Extracellular recordings were obtained from inferior colliculus (IC) neurons on young (2-month) and very old (greater than 2-year) CBA/J mice in response to contralateral tone and noise stimuli. The old mice had a small loss of spiral ganglion cells throughout the cochlea and moderate hearing loss, manifested as an elevation of neuronal thresholds throughout the IC. There was an age-related increase (3% to 22%) in 'sluggish' neurons (auditory, but poorly driven by sound); however, most neurons responded robustly to sound. Nine response types were derived from post-stimulus time histograms (PSTHs); all types were found in both age groups with no difference in their relative incidence. Sustained responses remained vigorous in old neurons, as indicated by spike counts and temporal discharge patterns. The percentage of neurons that were spontaneously active increased with age in the ventral IC (the area most sensitive to high frequencies, including most of the central nucleus) and decreased in the dorsal IC (the area most sensitive to lower frequencies, including much of the dorsal cortex). Parameters of response areas (range, upper frequency cutoff, best frequency, and rate-best frequency) showed modest age differences, while rate-level functions showed little age-related change. While a significant correlate of old age was attrition of IC neurons from the population capable of responding robustly to sounds, the majority of individual neurons demonstrated a remarkable degree of normalcy in their responses.

Action Potentials↗

Response properties of inferior colliculus neurons in middle-aged C57BL/6J mice with presbycusis.

Extracellular recordings were obtained from inferior colliculus (IC) neurons in young (2-month) and middle-aged (7-month; 12- to 13-month) C57BL/6J mice in response to contralateral tone and noise stimuli. An age-related progressive loss of spiral ganglion cells, most pronounced near the cochlear base, was observed in the mice, accompanied by severe high frequency hearing loss manifested as elevation of neuronal thresholds, especially in the ventromedial half of the IC. There was a small age-related increase (2% to 11%) in 'sluggish' neurons (auditory, but poorly driven by sound); however, most neurons were well-driven by suprathreshold stimuli. Nine response types were derived from post-stimulus time histograms; they were found in all age groups with little difference in their relative incidence. The percentage of neurons that were spontaneously active increased with age in the central nucleus but not in other subnuclei. Parameters of response areas (range, upper frequency range, best frequency, and rate-best frequency) showed pronounced age differences in the ventromedial half of the IC and minimal differences in the dorsolateral half of the IC. The percentage of neurons with nonmonotonic rate-level functions decreased with age, especially in the IC dorsal cortex.

Acoustic Stimulation↗

Acoustic startle response in young and aging C57BL/6J and CBA/J mice.

C57BL/6J (C57) mice demonstrate progressive age-related hearing loss during the first year of life, whereas CBA/J (CBA) mice lose little sensitivity through 18 months of age. The acoustic startle response (ASR) was measured in these strains to determine behavioral correlates of aging with and without presbycusis. The stimuli were tone pips (10-ms duration, 1-ms rise-fall) with frequencies of 4, 8, 12, 16, or 24 kHz at intensities of 70, 80, 90, or 100 dB SPL. ASR "thresholds" (the minimum SPL required to elicit ASRs more than 50% of the time) increased with age, and startle amplitudes became smaller in both strains. However, the changes in these startle parameters were much more pronounced in C57 mice, with middle to high frequencies (12-24 kHz) severely affected. The startle latencies at and above ASR "threshold" increased with age in C57 mice, but did not change in CBA mice. The CBA data indicate that aging, per se, has little effect on ASR parameters; the C57 data show that hearing loss is a cogent factor. However, ASR parameters of C57 mice are altered to a greater extent than expected, on the basis of the elevations of absolute sensory thresholds, particularly for middle frequencies (12-16 kHz). Both peripheral and central mechanisms are proposed to account for the discrepancy.

Aging↗

Morphometric study of the anteroventral cochlear nucleus of two mouse models of presbycusis.

The dimensions and volume of the anterior ventral cochlear nucleus (AVCN), the density and number of AVCN neurons, and the size of neuronal somata nuclei (in Nissl-stained tissue) were determined in two mouse models of age-related hearing loss: the C57BL/6J strain, which undergoes progressive chronic sensorineural hearing loss with onset during young adulthood, and the CBA/J, which demonstrates only moderate hearing loss with onset late in life. Frontal and horizontal AVCN sections, as well as cochleas, were analyzed in 4 C57 age-groups (1, 7, 12, 19+ months) and in 3 CBA groups (1, 10, 22 months). Within each strain no significant changes in AVCN dimensions or volume occur with aging. In C57 mice, packing density and cell number decrease between 1 and 7 months, but remain stable thereafter, despite chronic severe hearing impairment. CBA mice show a reduction in AVCN cell number and packing density only during the second year of life. In aging C57 mice, the size of spherical and perhaps globular cells increases, whereas the size of multipolar cells tends to decrease slightly. In CBA mice, all three AVCN cell types tend to decrease in size with aging. The early cell loss and cell size increases in C57 mice are most consistent in the dorsal (high frequency) region of the AVCN. Likewise, loss of cochlear spiral ganglion cells is most pronounced in the base of the cochlea, which provides input to this region. The data indicate that aging is associated with rather different central effects, depending on AVCN cell type, cochleotopic organization, genotype, and/or the type of peripheral hearing loss involved. The C57 and CBA AVCNs also differ in several aspects irrespective of age. The volume of AVCN and number of AVCN neurons are significantly greater in C57 mice.

Animals↗

Aging and the auditory brainstem response in mice with severe or minimal presbycusis.

Threshold, latency, and amplitude of the auditory brainstem response (ABR) were obtained with filtered noise pips in young and aging C57BL/6J mice (to 16-months), which undergo severe progressive age-related sensorineural hearing loss (presbycusis) and CBA/J mice (to 19-months), which show only mild loss late in life. Aging per se (CBA mice) is not associated with significant changes in ABR parameters. Presbycusis, in aging C57 mice, is associated with increased thresholds; there is a trend toward increased latencies, but only when threshold elevations are substantial. Amplitudes of early waves, but not late waves, decrease greatly in aging C57 mice. In young C57 mice, amplitudes of early ABR waves vary monotonically with intensity, while amplitudes of later waves (IV and V) have a relatively flat, or even nonmonotonic, relationship to intensity; in older C57 mice, all waves have monotonic intensity functions. ABR parameters are not affected by gender in either strain. The mouse models can help to clarify some inconsistencies in the human literature on aging and the ABR.

Age Factors↗

The influence of stimulus repetition on the acoustic startle response and on responses of inferior colliculus neurons of mice.

The acoustic startle response (ASR) and discharges of single units in the inferior colliculus (IC) were evaluated as a function of the repetition rate and trial (stimulus 1-10 at each rate) of intense noise bursts in mice. The amplitude of the ASR was inversely proportional to both rate and trial. The mean number of discharges for the sample population of units of the central nucleus (ICC) and the external nucleus (ICX) were also inversely proportional to stimulus rate. However, only ICX units were inversely proportional to trial (i.e. as was the ASR). When response properties of individual units were examined, a variety of profiles was observed with regard to rate and trial sensitivity: units were either not sensitive to stimulus rate, inversely sensitive, directly sensitive, or complexly sensitive. Superimposed on these rate classifications were trial sensitivity, with some units being insensitive to trial, directly sensitive, or inversely sensitive. The incidence of response types differed in some respects between ICC and ICX and these differences were, in general, consistent with the mean responses of the neuronal populations.

Acoustic Stimulation↗

Effects of aging, hearing loss, and anatomical location on thresholds of inferior colliculus neurons in C57BL/6 and CBA mice.

Multiple-unit threshold curves (MTCs) were obtained from inferior colliculus (IC) neurons across much of the (approximately 2-2.5 yr) life-span of two inbred mouse strains: the C57BL/6, which undergoes progressive age-related sensorineural hearing loss; and the CBA, which maintains good sensitivity until well into the second year of life. Tonotopic organization (the orderly dorsoventral arrangement of frequency sensitivity) is disrupted in the IC central nucleus (ICC) of aging C57 mice. Dorsal (low-frequency) MTCs change little during the first year of life, but in more ventral (high-frequency) regions high-frequency portions of MTCs are eliminated, best frequencies become lower, and low-frequency thresholds are reduced. These changes make the curves more similar to one another along the dorsoventral axis. During the second year of life, all thresholds become greatly elevated with neurons throughout the IC responding only to middle frequencies at very high intensities. In C57 mice, Q10 ratios (a measure of MTC tip sharpness) decline after 7 mo. The decline of Q10 with aging is associated with the age-related lowering of best frequencies and elevation of thresholds, both of which are positively correlated with smaller Q10s. The frequency range of C57 MTCs begins to decrease at 14 mo of age, when hearing loss is quite severe at all frequencies. In CBA mice, the above changes are minimal or do not occur even in 22 mo olds, which have moderate loss of sensitivity across all frequencies. Even in young mice (prior to demonstrable cochlear pathology in C57 mice), there are differences in MTCs between the two strains employed, with sensitivity of CBA mice being "shifted" toward higher frequencies. Age-related changes in MTC properties depend on the pattern of hearing loss (e.g., high frequency vs. flat) and the dorsoventral location of neurons within the ICC.

Acoustic Stimulation↗

Projections from the anterior ventral cochlear nucleus to the central nucleus of the inferior colliculus in young and aging C57BL/6 mice.

Projections from the anterior ventral cochlear nucleus (AVCN) to the central nucleus of the inferior colliculus (ICC) were studied in young and aging C57BL/6 mice. The latter animals demonstrate progressive loss of hearing. Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the inferior colliculus and retrograde transport to the AVCN sections, quality of labelling, number of labelled neurons adjusted for injection size, or topographic organization of projections. Thus, despite progressing loss of auditory sensitivity, chronic profound hearing loss (oldest animals), and aging, projections from AVCN to ICC remain stable.

Aging↗

Changes in frequency representation in the auditory system of mice with age-related hearing impairment.

Aging C57BL/6 mice show a progressive decline in sensitivity to sound, beginning with high frequencies. In the inferior colliculus (IC), tonotopic organization--the orderly representation of frequency from low to high along the dorsoventral dimension--shows marked changes. No neurons respond to high frequencies, most respond best to a restricted range of frequencies, and ventral neurons become responsive to low frequencies. These age-related response alterations have implications for hearing problems of aging humans.

Acoustic Stimulation↗

Excitability of auditory neurons in the dorsal and ventral cochlear nuclei of DBA/2 and C57BL/6 mice.

Extracellular response properties were studied in neurons of the dorsal and ventral divisions of the cochlear nucleus (DCN and VCN, respectively) of DBA/2 (DBA) and C57BL/6 (C57) mice. Mice of the former inbred strain show susceptibility to audiogenic seizures and have severe high frequency hearing loss when young; mice of the latter strain do not. Whereas afterdischarges had been readily observed in the inferior colliculus of DBA mice in a previous study, they were never observed in the cochlear nucleus. The incidence of nonmonotonic intensity functions, the slopes of intensity functions, and the incidence of inhibition in response areas indicated that inhibition was diminished in the DCN of DBA mice. However, in the VCN, these response properties did not differ between the two strains. There appeared to be an "amplification" of excitability (i.e., attenuation of inhibition) from VCN to DCN to inferior colliculus in DBA mice.

Acoustic Stimulation↗

The acoustic startle response in DBA/2 and C57BL/6 mice: relationship to auditory neuronal response properties and hearing impairment.

The acoustic startle response (ASR) was elicited with tone pips in sensorineural hearing-impaired DBA/2 mice and in non-impaired C57BL/6 mice. The influence of stimulus frequency and intensity on ASR amplitude varied as a function of both strain and age. Previous neurophysiological findings indicate that ASR amplitude is correlated with the proportion of neurons in the cochlear nucleus and inferior colliculus that respond to the ASR stimulus frequencies and to the excitability of neurons in these structures. ASR amplitude is not highly correlated with threshold sensitivity. These observations suggest several neural correlates of ASR amplitude and have implications regarding central neuronal response properties associated with sensorineural hearing loss.

Acoustic Stimulation↗

Frequency difference limens of C57BL/6 and DBA/2 mice: relationship to auditory neuronal response properties and hearing impairment.

Frequency difference limens (DLs) were measured in DBA/2 and C57BL/6 mice using an avoidance conditioning procedure and were viewed in relation to previously obtained neurophysiological data. DRA mice had significantly smaller DLs at 12 and 16 kHz, despite progressive sensorineural hearing loss and disrupted tonotopic organization characteristic of this strain. C57 mice had smaller DLs at 8 kHz. Several inferior colliculus (IC) neuronal response properties, that may be related to DL performance, differ between strains. Compared to C57s, a large proportion of DBA neurons respond to 12 and 16 kHz, many more best frequencies (BF, the frequency for which a neuron is most sensitive) fall between 10 and 20 kHz, response ranges are narrow, and neural intensity functions are steep. For C57 mice, a large proportion of neurons respond to 8 kHz, and more neurons have BFs between 5 and 10 kHz.

Animals↗

Abnormal tonotopic organization in the ventral cochlear nucleus of the hearing-impaired DBA/2 mouse.

The representation of sound frequency by auditory neurons (tonotopic organization) was evaluated in the ventral cochlear nucleus (VCN) of DBA/2 mice, a strain with impaired sensitivity to the highest and lowest frequencies heard by normal mice. Tuning curves were obtained from multiple-unit activity (MUA) and compared with those of C57 mice, which do not have severe hearing loss. Tuning curves in the C57 VCN displayed the dorsoventral progression from high- to low-frequency sensitivity that is typical of mammals. By contrast, tuning curves of DBA mice varied little as a function of dorsoventral location, and most MUA thresholds were lowest for frequencies within a narrow range (about 12-16 kHz). Thus, normal tonotopic organization is absent in the DBA mouse's VCN. In addition, because of the consistently low thresholds for 12-16 kHz tones in DBA MUA, mean thresholds for these frequencies are lower than those of C57 MUA in the dorsal and ventral portions of the VCN.

Animals↗

Noise-induced hearing loss can alter neural coding and increase excitability in the central nervous system.

Responses of auditory neurons in the inferior colliculi of mice were studied longitudinally before and shortly after each animal was exposed to intense noise. Noise exposure caused expected losses in auditory sensitivity, but in 31 percent of the neurons studied, unexpected alterations of temporal patterns of action potentials were observed: certain suprathreshold stimuli that had evoked only transient "onset" responses or inhibition of spontaneous discharges prior to noise exposure came to elicit sustained excitation after exposure. Thus, noise-induced hearing loss can be associated with increases in neural responsivity and alterations of normal neural coding processes.

Acoustic Stimulation↗

Inverse relationship between whole brain monoamine levels and audiogenic seizure susceptibility in mice: failure to replicate.

Whole brain levels of 5-HT and NE in audiogenic seizure susceptible DBA mice were compared with those of the nonsusceptible C57BL/6 strain at different ages and in two separate laboratories that used different assay procedures. Contrary to previous reports, there were not significant differences between the susceptible and nonsusceptible animals in whole brain levels of either amine at the age of peak seizure susceptibility. Differential stress associated with capturing the susceptible mice had no effect on brain levels of NE. The data question the suggestion that deficits in brain monoamine transmission capable of being indexed by lower whole brain levels of NE and/or 5-HT play a role in genetically determined susceptibility to audiogenic seizures.

Acoustic Stimulation↗

Ontogeny of the acoustic startle response in C57BL/6J mouse pups.

A cross-sectional design was used to study the development of acoustic startle behavior in C57BL/6J mice from the approximate onset of hearing (12 days) to 17 days of age. Startle incidence and latency were recorded in response to 5-, 7-, 10-, 15-, and 20-kHz tones each presented at 80, 90, and 100 dB (SPL). From 12 to 17 days of age, higher frequency and lower intensity tones became increasingly effective in eliciting the acoustic startle response. In addition, startle latency decreased substantially, and response incidence became more sensitive to changes in tone intensity and tone frequency. This rapid ontogeny of the acoustic startle response closely parallels previously demonstrated neurophysiological development of the mouse pup auditory system.

Aging↗