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.

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.

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.

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.

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.

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.

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.

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.