Colony-Wide Analysis of Mouse Auditory Brainstem Responses (II): Maturational, Gender and Aging Effects in C57Bl/6J and

1. 2 mo 5-7 mo 8-14 mo 15-22 mo 23-27 mo 28-34 mo 2 mo 3 mo 5 mo 7 mo 8 mo ABR Ratio Plots ABR Ratio Plots Level (dB SPL) Level (dB SPL) Difference in Ratio Male - Female Difference in Ratio Male - Female Level (dB SPL) Level (dB SPL) 35 M - 35 F 11 M - 10 F 27 M - 21 F 9 M - 9 F 41 M - 22 F 22 M - 17 F 16 M - 20 F 19 M -17 F 1 M - 8 F 3 M - 7 F 0 M - 8 F Colony-Wide Analysis of Mouse Auditory Brainstem Responses (II): Maturational, Gender and Aging Effects in C57Bl/6J and CBA/CaJ Mice Paul Allen1, John Housel2, Jason Moore1, William O'Neill1,2, Peter Rivoli1, James Ison1 1Department of Brain & Cognitive Sciences, University of Rochester;2 Dept of Neurobiology & Anatomy, University of Rochester School of Medicine and Dentistry; Rochester, NY ARO 2005 433 Introduction CBA/CaJ C57Bl/6J CBA/CaJ and C57BL/6J mice provide useful models for contrasting rapid degenerative vs. slow age-related hearing loss. The descriptions of ABR hearing measures in these mice are mostly obtained in small groups (save for Li and Borg, 1991), and concerned with thresholds (save for Hunter and Willott, 1987). Our colony at the University of Rochester provides these mice to investigators focused on age-related changes in complex auditory processing. Both threshold and superthreshold ABR measures are taken on many mice at ages that meet the special needs of particular protocols. Here we describe ABR measures collected over 6 years, in a total of 570 CBA mice (267F, 303M) and 353 C57 (161F, 192M), most born in the vivarium from Jackson Lab breeding stock. The youngest mice for which records are available were 27 days of age while the oldest mice were 1046 days of age for the CBA (n = 2) and 787 days of age for the C57 (n=2). The data we present are grouped in age bins providing sufficiently large samples of males and females to minimize potential cohort and procedural differences across time. ABR Thresholds: 1 to 12 Months of Age ABR Thresholds from 1 to 30 Months of Age Left: “Classic” frequency across age Right: Age effect across frequency 1) Initial slow loss for all frequencies, then delayed abrupt loss, higher first 2) Old females are slightly more sensitive to low frequencies • No threshold loss (and possible maturational gain?) up to 14 mo of age • Progressive loss, equal across frequency, beyond 14 mo of age • No systematic sex differences Changes in ABR Waveforms with Hearing-loss Changes in ABR Waveforms with Age • Reduction in P1 amplitudes (as seen for 12kHz, 90dB SPL) • Lengthening of Inter-peak intervals • (Note that wave forms are aligned on P1) • Subtle changes in ABR waveform with age • Change in appearance of P1a/N1 complex • No sex effect on ABR waveforms Reduction in P1 amplitude (shown for 12kHz, 90 dB) (Note that waveforms have been aligned on P1) ABR waveforms change with hearing-loss Inter-peak intervals remain stable (except P2, P4) Females have slightly larger ABR peaks (Head size?) Aging-related Changes in Superthreshold ABR Changes in Superthreshold ABR with Hearing-loss Subjects and Methods CBA/CaJ: (710 recordings, 388 from Males, 322 from Females) C57Bl/6: (484 recordings, 244 from Males, 240 from Females) Auditory brainstem response (ABR) Routinely measured in conjunction with behavioral, electrophysiological or histological experiments For methods see presentation 437 Multiple ABRs were accepted for an animal only if there was a minimum of 60 days between recordings Animals undergoing drug treatment etc. are excluded Superthreshold ABR is assessed via signal to noise S/N ratio calculated from the RMS of 2kHz high-pass filtered waveforms RMS windows: Pre-response = 0.75-1.5 ms, Evoked Response = 1.5-10 ms S/N calculated for a subset of mice (using TDT System II apparatus) CBA/CaJ (N=259, 145 Males and 114 Females) C57Bl/6 (N=99, 39 Males and 60 Females) • Superthreshold S/N ratio plots show substantial decline with age in first year of life, despite negligible threshold changes • Central neural aging? • Artifact of changes in head size, or dielectric properties of cranium? • Possible weak female advantage seen in S/N color plots up to 22 months • S/N ratios for 90 dB highlight the progressive decline into old age and lack of systematic sex differences with age and frequency Superthreshold S/N ratios show progressive high frequency hearing loss in parallel with the elevated ABR thresholds. The 90 dB S/N data show a progressive decline with age for all frequencies Possible female advantage is seen in S/N ratios above threshold, and is consistent with threshold data The initial age-related gradual hearing loss across frequencies is consistent with, e.g., Hequembourg & Liberman, (2001), but the data favoring female over male inconsistent with Willott & Bross (2004) or Henry (2002). ABR Ratio vs Age 90dB SPL ABR Ratio vs Age 90dB SPL Difference in Ratio Male - Female Difference in Ratio Male - Female Supported by NIA Grant #AG09524 and The Schmitt Program on Integrative Brain Research