1. Cross-Spectral Channel Gap Detection in the Aging CBA Mouse Jason T. Moore, Paul D. Allen, James R. Ison Department of Brain & Cognitive Sciences, University of Rochester, Rochester, NY ARO 2005 432 Introduction Methods Experiment 1: The pre-gap marker (M1) and the post-gap marker (M2) were centered at either 8 or 32 kHz, yielding two within-channel conditions and two between-channel conditions. The gap duration ranged from 0 to 30 ms. Experiment 2: M1 was centered at either 9.51, 16, or 26.91 kHz, while the center frequency for M2 ranged from 6.7 to 38 kHz, yielding 3 within-channel condition and 30 between-channel conditions for each M1 frequency. The gap duration was either 0 or 10ms. Experiment 3: M1 and M2 were always centered at the same frequency, but this center frequency ranged from 6.7 to 38 kHz, yielding 11 within-channel conditions. The gap duration was either 0 or 10 ms. Gap detection is optimal when the auditory stimuli preceding and following the gap are spectrally similar (within-channel signals), but can still occur to a lesser extent with between-channel signals (Formby and Forrest, 1991; Oxenham, 2000). More recent studies using within-channel signals have shown that temporal acuity degrades with age in mice as it does in humans (Barsz et al, 2002; Allen et al., 2003; and note that age does not affect noise pulse detection). To our knowledge nothing is known about how aging affects between-channel gap detection. This series of experiments was performed in order, first, to compare the aging CBA mouse’s performance on within- and between- channel detection tasks (Expt 1); second, to determine how between-channel gap detection is affected by the spectral components of the auditory signals (Expt 2); and third, to provide data directly comparing the spectral dependence of between- channel and within-channel gap detection (Expt 3). Within-Channel: The 2- and 12-month old CBAs performed similarly on both within-channel conditions, with the low-frequency condition requiring a longer gap to achieve a comparatively lower level of maximal inhibition. The 24-month CBAs exhibited inhibition from gaps only in the high-frequency within-channel condition, and the gap detection threshold was higher than that of the younger mice. Within-Channel Gap Detection (left): Young and middle-aged mice had significant inhibition to all conditions except for the lowest center frequency (6.7 kHz), while the old mice detected the 10ms gap only when the two markers were centered at higher frequencies (22.6-38 kHz ). Comparison with ABR Thresholds (right): The frequency range that provides the lowest ABR thresholds (12-16 kHz) is spectrally distinct from the range that provides best temporal acuity (22.6 and 26.9 kHz). The mice that were used to determine ABR thresholds (N=23, 31, 41 for 2mo, 12mo, 24mo) were not tested in the behavioral portion of this experiment. Solid lines represent the frequency range of best within-channel gap detection. Experiment 3: Within-channel gap detection across frequencies Experiment 1: High frequency within-channel gaps have the lowest detection thresholds Experiment 2: Aging-related loss of cross-spectral channel gap detection Subjects: Three groups, each containing 16 CBA/CaJ mice: young adult (2 months), middle-aged (12 months), and old (24 months). Auditory Stimuli and Recording: Gap detection was quantified by measuring the magnitude of a mouse’s acoustic startle reflex (ASR) via reflex modification. All stimuli were ½-octave band filtered pink noise and were presented at 70 dB SPL in the presence of a constant 50 dB pink noise background. The eliciting stimulus (ES) was a 30 ms, 110 dB noise burst and was always presented 50 ms after the end of the gap. 10 trials were performed for each condition, with a mean inter-trial interval of 20 sec. ES M1 M2 Inhibition Due to Frequency Swap: While within each age group the spectral contents of the markers had little effect on the amount of swap-induced inhibition, the frequency swap proved to be a salient inhibitory stimulus with a strong interaction between frequency and age. When M1 was a low frequency, both the young and middle-aged mice perform very similarly, while when M1 was a high frequency, the frequency swap was less inhibitory to the young mice. Inhibition Due to Gaps: Old mice showed no consistent inhibition in the between-channel conditions. The 2-month old mice were better able to detect low-to-high spectral swaps than the 12-month old mice, while the two age groups performed similarly in high-to-low spectral swaps. Discussion Gap detection is dependent on the spectral contents of the pre- and post-gap auditory stimuli. Within- channel gaps were easier for the mice to detect at shorter gap durations and these gaps resulted in greater inhibition of the startle reflex than between-channel gaps. For young and middle-aged mice, the preferable between-channel condition was a low frequency marker preceding the gap and a higher frequency marker following the gap, compared to the reverse, and a high-frequency M2 was most important for gap detection. However, aging leads to an almost complete loss of the ability to detect gaps between spectrally dissimilar signals; old mice were only able to appreciably detect gaps in high-frequency within-channel conditions. While mice have their best ABR thresholds at 12-16 kHz, they performed best at gap detection when the markers contained higher frequency components (22-26 kHz), providing further support to the hypothesis that the aging-related loss of temporal acuity is at least partly independent of sensorineural hearing loss. Despite elevated ABR thresholds for high frequencies, older mice require the presence of higher frequencies to perform gap detection, indicating that aging virtually eliminates the mouse’s ability to use low and mid frequencies as cues for gap detection. Between-Channel: The old mice were not able to detect gaps in either between-channel condition. Both of the younger groups performed better in the low-to-high frequency condition than in the high-to-low condition. Supported by NIA Grant #AG09524 and the de Kiewiet Fellowship