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Hearing dysfunction has been associated with Alzheimer's disease (AD) in humans, but there is little data on the auditory function of mouse models of AD. Furthermore, characterization of hearing ability in mouse models is needed to ensure that tests of cognition that use auditory stimuli are not confounded by hearing dysfunction. Therefore, we assessed acoustic startle response and pre-pulse inhibition in the double transgenic 5xFAD mouse model of AD from 3-4 to 16 months of age. The 5xFAD mice showed an age-related decline in acoustic startle as early as 3-4 months of age. We subsequently tested auditory brainstem response (ABR) thresholds at 4 and 13-14 months of age using tone bursts at frequencies of 2-32 kHz. The 5xFAD mice showed increased ABR thresholds for tone bursts between 8 and 32 kHz at 13-14 months of age. Finally, cochleae were extracted and basilar membranes were dissected to count hair cell loss across the cochlea. The 5xFAD mice showed significantly greater loss of both inner and outer hair cells at the apical and basal ends of the basilar membrane than wild-type mice at 15-16 months of age. These results indicate that the 5xFAD mouse model of AD shows age-related decreases in acoustic startle responses, which are at least partially due to age-related peripheral hearing loss. Therefore, we caution against the use of cognitive tests that rely on audition in 5xFAD mice over 3-4 months of age, without first confirming that performance is not confounded by hearing dysfunction.

Previous psychophysical work on sound localization in humans has proposed that a midline channel be added to the current two-channel model of mammalian sound localization mechanisms. Evidence for this third channel has been found in interaural time difference (ITD) studies with low-frequency tones, and interaural level difference (ILD) studies with both high- and low-frequency tones. The latter is interesting because it suggests that, despite the fact that low frequencies do not generate significant ILDs for humans in natural settings, there is a constancy of ILD coding mechanisms across the frequency domain. To complement this finding, the present study sought to determine whether the three-channel model holds for ITDs at high frequencies. In three experiments, a selective adaptation paradigm was used in combination with transposed tones to probe for the existence of three (left, right, and midline) perceptual channels for sound source azimuth. The experiments provided evidence for lateral hemifield ITD channels but little evidence for a midline ITD channel at high frequencies.

Two experiments measured human sensitivity to temporal jitter in 25-click trains with inter-click intervals (ICIs) between 5 and 100 ms. In a naturalistic experiment using wideband clicks, jitter thresholds were a nonmonotonic function of ICI, peaking for ICIs near 40-60 ms. In a subsequent experiment, clicks were high-passed and presented against a low-frequency noise masker. Jitter threshold vs ICI functions lost the positive slope over short ICIs but retained the negative slope at long ICIs. The same behavior was seen in click rate discrimination tasks. Different processes mediate regularity analysis for click trains with ICIs above and below 40-60 ms.

The current understanding of mammalian sound localization is that azimuthal (horizontal) position assignments are dependent upon the relative activation of two populations of broadly-tuned hemifield neurons with overlapping medial borders. Recent psychophysical work has provided evidence for a third channel of low-frequency interaural time difference (ITD)-sensitive neurons tuned to the azimuthal midline. However, the neurophysiological data on free-field azimuth receptive fields, especially of cortical neurons, has primarily studied high-frequency cells whose receptive fields are more likely to have been shaped by interaural level differences (ILDs) than ITDs. In four experiments, a selective adaptation paradigm was used to probe for the existence of a midline channel in the domain of ILDs. If no midline channel exists, symmetrical adaptation of the lateral channels should not result in a shift in the perceived intracranial location of subsequent test tones away from the adaptors because the relative activation of the two channels will remain unchanged. Instead, results indicate a shift in perceived test tone location away from the adaptors, which supports the existence of a midline channel in the domain of ILDs. Interestingly, this shift occurs not only at high frequencies, traditionally associated with ILDs in natural settings, but at low frequencies as well.

Heffner (2004) provided an overview of data on the evolutionary pressures on sound localization acuity in mammals. Her most important finding was that sound localization acuity was most strongly correlated with width of field of best vision. This correlation leaves unexplained the mechanism through which evolutionary pressures affect localization acuity in different mammals. A review of the neurophysiology of binaural sound localization cue coding, and the behavioural performance it supports, led us to two hypotheses. First, there is little or no evidence that the neural mechanisms for coding binaural sound location cues, or the dynamic range of the code, vary across mammals. Rather, the neural coding mechanism is remarkably constant both across species, and within species across frequency. Second, there is no need to postulate that evolutionary pressures are exerted on the cue coding mechanism itself. We hypothesize instead that the evolutionary pressure may be on the organism's ability to exploit a ‘lower envelope principle’ (after Barlow, 1972 ).

Two hallmark features of auditory neuropathy (AN) are normal outer hair cell function in the presence of an absent∕abnormal auditory brainstem response (ABR). Studies of human AN patients are unable to determine whether disruption of the ABR is the result of a reduction of neural input, a loss of auditory nerve fiber (ANF) synchrony, or both. Neurophysiological data from the carboplatin model of AN reveal intact neural synchrony in the auditory nerve and inferior colliculus, despite significant reductions in neural input. These data suggest that (1), intact neural synchrony is available to support an ABR following carboplatin treatment and, (2), impaired spike timing intrinsic to neurons is required for the disruption of the ABR observed in human AN.

Groups of rats were chronically exposed to a 1.0-g/L caffeine solution for 5, 10, 15 or 20 days. Upon removal of caffeine, rats were given brief exposure to a novel flavour CS (withdrawal CS) followed by 12 days of plain water and then brief exposure to a second flavour CS (neutral CS). Only rats exposed to 20 days of caffeine strongly preferred the neutral CS to the withdrawal CS in a 2-bottle test. In Experiment 2, groups of rats were chronically exposed to caffeine at one of four concentrations (1.0, 0.5, 0.25, or 0.125 g/L) for 21 days, after which withdrawal and neutral CSs were established. Only rats that drank the highest caffeine concentration, 1.0 g/L, preferred the neutral CS to the withdrawal CS. This suggests that long exposure to a strong caffeine solution is required in order to induce dependence in rats such that a CS associated with the withdrawal of caffeine becomes avoided.

Rats were given 21 days of chronic oral caffeine. A novel flavor (Maintenance CS) was then paired with the continuation of caffeine, and a second flavor (Withdrawal CS) was paired with caffeine removal. Rats avoided the Withdrawal CS, and drank more of the Maintenance CS in a two-bottle test, suggesting that removing caffeine had induced withdrawal. The value of the Maintenance CS was investigated by comparing it to a novel flavor paired with water (Neutral CS). In a series of two-bottle tests, the Maintenance and Neutral CSs were equivalent when pitted against each other, and both were preferred to the Withdrawal CS. These results demonstrate that conditioned flavor avoidance is a useful procedure in assessing caffeine withdrawal, and by inference dependence, produced by chronic oral consumption.

Male CD-1 mice were given a biconditional discrimination task with four odors; A, B, C, and D. Mice were presented with odor compounds AC+, BD+, BC−, AD− for thirteen days. Pieces of odorized filter paper were placed in the bottom of odor pots and covered with bedding. On reinforced AC and BD trials, sugar was buried in the bedding, and on nonreinforced AD and BC trials no sugar was present. Following training, simultaneous nonreinforced tests were given between AD and AC, and between BC and BD. The mice spent more time digging in the previously reinforced odor compounds than in the previously nonreinforced compounds. In a second experiment, mice were conditioned to dig in AC+ and not BD−. In a subsequent test with the separate elements they dug more in A and C than in B and D, indicating that the biconditional discrimination had not been solved on the basis of complete perceptual blending. The data demonstrate that mice are capable of olfactory configural learning when solving a biconditional discrimination.

Neurophysiological and psychophysical evidence has driven the formulation of a hemifield model of mammalian sound localization in which the perceived location of a stimulus is based on the relative activity of two hemifield-tuned azimuthal channels that are broadly responsive to contralateral auditory space and have overlapping medial borders. However, neurophysiological work in mammals has consistently found neurons selective for sound sources at the midline, which may indicate the existence of a third, ‘midline’, perceptual channel. In three experiments, the existence of three (left, right, midline) perceptual channels for azimuth in man was examined using auditory selective adaptation paradigms. If no midline channel exists, exposure to highly lateralized, symmetrical adaptator frequencies should not result in a shift in the perceived intracranial location of subsequent test tones away from the adaptors because the relative activation of the two hemifield channels will remain the same. Rather, our results indicate a shift in perceived test tones towards the azimuthal midline. This result can best be explained by a perceptual/neural channel tuned to sounds located along the midline. The present study gives the first psychophysical evidence of a midline channel serving human auditory localization, adding to the earlier evidence on the same point from animal neurophysiological studies.