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Minimum Audible Angle Measured in Young and Old CBA Mice ..

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Minimum Audible Angle Measured in Young and Old CBA Mice ... Paul D. Allen, Jordan Bell, Navin Dargani, Catherine A. Moore, Carolyn M. Tyler, James R. Ison ... – PowerPoint PPT presentation

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Title: Minimum Audible Angle Measured in Young and Old CBA Mice ..


1
Minimum Audible Angle Measured in Young and Old
CBA Mice Using Prepulse Inhibition of
Startle Paul D. Allen, Jordan Bell, Navin
Dargani, Catherine A. Moore, Carolyn M. Tyler,
James R. Ison Department of Brain Cognitive
Sciences, University of Rochester, Rochester, NY
ARO 2003 353
Experiment 2 Age Effect on Speaker Swap
Experiment 3 Frequency Effect on Speaker Swap
Introduction
Experiment 1 Broad Band Noise Speaker Swap
  • Auditory spatial acuity supports sound
    localization and is used to improve communication
    in noisy environments via unmasking of spatially
    separable sound sources
  • The CBA mouse is a successful animal model of
    presbycusis, displaying changes in auditory
    temporal processing with age analogous to those
    observed in humans, which have been linked to
    deficits in speech perception especially in
    noisy backgrounds
  • In this study we wanted to find out if parallel
    changes in auditory spatial acuity occur with age
    in the CBA mouse, using a novel application of
    prepulse inhibition of acoustic startle
  • Startle response amplitude is modulated by prior
    perturbation of the acoustic environment
    (inhibition)
  • Does a change in spatial location of a continuous
    sound source cause prepulse inhibition?
  • Can we estimate a minimum audible angle for the
    mouse in this way?
  • Previous behavioural measures of spatial acuity
    in the mouse
  • 7-15 in 2 month old house mouse (Ehret Dreyer,
    1984)
  • 19 in the 2 month old C57 mouse (Heffner, Koay,
    Heffner, 2001)
  • How does detection of a change in spatial
    location depend on stimulus duration?
  • How do these parameters change with age?
  • What are the neural bases for age-related changes
    in spatial acuity in the mouse?
  • Question 1
  • Is 180 speaker swap inhibitory?
  • 180 speaker swap was compared with simple noise
    offset and onset (i.e. S1 or S2 alone)
  • 3 month old mice
  • Off (N7), On (N6), Swap (N13)
  • Inhibition starts rapidly after noise Offset at
    1ms it is marginally significant, but highly
    significant from 2 to 300 ms
  • Onset shows marginally significant facilitation
    out to 5 ms, then highly significant inhibition
    from 10 to 200 ms
  • 180 speaker swap is significant from 5 to 300
    ms, with a hint of facilitation at 1ms
  • 180 speaker swap has inhibitory effect
    intermediate to noise offset and onset (dashed
    grey curve shows simple average of on- and offset
    data)
  • The sum of monaural cues?
  • Intervals with non-linear averaging may reflect
    binaural processing
  • Question 2
  • Given that 180 speaker swap is inhibitory, how
    does inhibition depend on the angular separation
    of the speakers?
  • Bringing speakers together reduces inhibitory
    effect of swap and delays ISI functions
  • Smaller angles have longer ISI to peak inhibition
    and maximal inhibition is reduced
  • Longer ISI required for significant inhibition
  • Window of optimal inhibition is reduced at
    smaller angles 60-100ms at 15
  • At a given ISI the effect size increases with the
    angular separation
  • 5ms only 180 provides significant inhibition
  • 3 age groups
  • 6 month old (N12)
  • 12 month old (N12)
  • 24 month old (N18)
  • Same design as Experiment 1, except minimum angle
    is 7
  • None of the groups show significant inhibition
    for the 7 swap
  • Compared with 3 month old data, ISI functions
    shift progressively later with age
  • Size of inhibitory effect is reduced with age
    even when it is reliably generated by large
    angular separations
  • Duration of optimum inhibition is reduced as
    longer ISI is required in old mice for
    inhibition, but inhibition does not persist
    longer
  • 6 month old mice (N12)
  • 70dB octave band carriers with 2ms on/offset
    shaping and 50dB broadband floor to mask
    transients
  • Swap of lower octaves (2-4 and 4-8 kHz) does not
    provide inhibition
  • 8-16 kHz does provide inhibition, but only at
    large angles
  • 16-32 has inhibition at this ISI that accounts
    for most of the response seen to swap of
    broadband noise, but the effect of frequency band
    on ISI is unclear
  • Masker noise and shaping of stimuli might also
    reduce inhibition, and account for the difference
    between broadband and 16-32 kHz

Discussion Here we demonstrate that swapping the
source of continuous noise between two speakers
causes prepulse inhibition of startle in CBA
mice, and since inhibition scales with angular
separation, the technique can provide behavioral
measures of minimum audible angle (MAA). These
data indicate that in the 3 month old CBA mouse
MAA at 0 degree azimuth is between 7 and 15, but
this resolution requires 60 to 100ms of
processing, with shorter ISIs yielding coarser
resolution. These results agree with previous
behavioral estimates of MAA in the mouse, and the
importance of sufficient ISI for inhibition to
develop maximum sensitivity is analogous to the
minimum integration time required for optimal MAA
in human psychoacoustics. The rapid onset of
inhibition when angular separation is large, but
not when it is small, indicates that monaural
cues at each ear are sufficient to alert the
auditory system to a change in the acoustic
environment, while the longer ISI required for
inhibition when angular separation and hence
monaural difference cues are reduced, suggests
that binaural processing of inputs to the two
ears is needed to detect the change in sound
source location. The 3rd experiment using octave
bands of noise shows that low frequency carriers
are ineffective in producing inhibition,
suggesting that ILDs provide the cues for spatial
discrimination. This result is in accord with the
mouse having a well developed LSO and atrophied
MSO. Alternatively, over this same frequency
range the mouse pinna produces spectral notches,
which might serve as a separate cue for change in
spatial location, mediated by DCN processing.
This could be tested using narrow band or pure
tone stimuli. There is a systematic increase with
age in the ISI needed to obtain a particular
level of auditory spatial resolution, and the
magnitude of the inhibition produced at a given
ISI and angle decline with age, particularly from
12 to 24 months of age. This finding suggests an
ageing effect which could worsen presbycusis by
diminishing binaural unmasking - the aging
localization system gradually ceases to provide
sufficient spatial resolution in the time
available for unmasking to be effective.
Methods
  • Subjects CBA/CaJ mice 3, 6, 12, 24 months old
  • Mice held in acoustically transparent wire cage
    mounted to a platform and accelerometer
  • Startle eliciting stimulus (ES) delivered
    overhead (120dB SPL, 15 ms broadband noise burst)
  • Startle response recorded from accelerometer (RMS
    100ms window, post-ES)
  • Spectrally-matched high-frequency speakers (TDT
    ES1) located 45cm from the mouse head
  • Angular separations 180, 90, 45, 22.5, or 15
    (7 in Experiments 2 and 3)
  • Cage oriented with head facing mid-line of two
    speakers
  • Continuous broadband noise (60 dB SPL, 1-50kHz)
    presented from one speaker (min 15s)
  • Prepulse is noise-swap between speakers at set
    inter-stimulus interval (ISI) prior to ES
  • ISI conditions 1, 2, 5, 10, 20, 30, 40, 50, 60,
    100, 150, 200, 300 ms, two no-prepulse controls,
    and a no-startle, no-swap activity control
  • Speaker angle is fixed in each session
    (counterbalanced design) with 11 presentations of
    each condition, block randomized
  • Inhibition calculated relative to no-prepulse
    controls

Supported by NIA Grant AG09524 and The Schmitt
Program on Integrative Brain Research
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