ARO 2003
353
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
• 180° speaker swap was compared with
simple noise offset and onset (i.e. S1 or S2
alone)
Single Off
Single On
180 Swap
80
60
40
• 3 month old mice
1
2
5
10
20 30
ISI (ms)
60 100
300
•Can we estimate a minimum audible angle for the mouse in this way?
80
40
20
• Spectrally-matched high-frequency speakers
(TDT ES1) located 45cm from the mouse head
2
5
10
20 30
ISI (ms)
60 100
300
90
45
15
C
• Speaker angle is fixed in each session
(counterbalanced design) with 11 presentations of
each condition, block randomized
• Inhibition calculated relative to no-prepulse controls
300
Angular Shift : 90 
• 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
C
1
2
60
5
10 20 30
ISI (ms)
60 100
300
• Duration of optimum inhibition is
reduced as longer ISI is required in old
mice for inhibition, but inhibition does
not persist longer
Angular Shift : 45 
180
40
1
2
5
10
20 30
ISI (ms)
60 100
300
• Smaller angles have longer ISI to peak
inhibition and maximal inhibition is reduced
-20
10 ms
50 ms
50
• 5ms only 180° provides significant
inhibition
25
• At 10ms, 22.5 ° is marginally significant
C
1
2
5
10 20 30
ISI (ms)
60 100
15
22.5
45
90
Angular Separation (degrees)
180
• Minimum Audible Angle depends on ISI:
optimum duration suggests MAA <15°
45
1
2
5
10
20 30
ISI (ms)
60 100
300
20
0
3 mo
6 mo
12 mo
24 mo
100
40
20
10
5
-20
C
1
2
60
5
10 20 30
ISI (ms)
60 100
300
15
Angular Shift : 7 
75
6 mo
12 mo
24 mo
40
20
22.5
0
45
Angle ()
ISI = 50 ms
90
180
C
1
2
5
10 20 30
ISI (ms)
60 100
300
20
10
0
-10
7
22.5
45
90
Angular Separation (degrees)
• 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
180 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 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 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.
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.
25
0
-20
30
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.
3 mo
6 mo
12 mo
24 mo
50
40
• 70dB octave band carriers with 2ms
on/offset shaping and 50dB broadband
floor to mask transients
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.
Angular Shift : 22.5 
40
ISI = 50 ms
Broadband (Expt 2)
2-4 kHz
4-8 kHz
8-16 kHz
16-32 kHz
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.
Solid lines show ISI times producing significant inhibition
Dots show ISI times leading to marginally significant inhibition
C
300
• At 50ms, 15° is marginally significant
0
3 month old
6 month old
12 month old
24 month old
22.5
60
• At a given ISI the effect size increases with
the angular separation
5ms
90
15
• Window of optimal inhibition is reduced at
smaller angles: 60-100ms at 15°
75
20
0
• Longer ISI required for significant inhibition
% Inhibition
• 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
•Intervals with non-linear averaging may
reflect binaural processing
• Bringing speakers together reduces
inhibitory effect of swap and delays ISI
functions
• Cage oriented with head facing mid-line of two
speakers
• Prepulse is noise-swap between speakers at set
inter-stimulus interval (ISI) prior to ES
60 100
20
-20
Given that 180° speaker swap is
inhibitory, how does inhibition depend
on the angular separation of the
speakers?
22.5
• Continuous broadband noise (60 dB SPL, 1-50kHz)
presented from one speaker (min 15s)
10 20 30
ISI (ms)
Angular Separation
1
180
• Angular separations: 180, 90, 45, 22.5, or 15° (7° in
Experiments 2 and 3)
5
0
% Inhibition
• Startle response recorded from accelerometer
(RMS 100ms window, post-ES)
2
1st ISI with q>2 (ms)
C
Question 2:
Angular Separation
• Startle eliciting stimulus (ES) delivered overhead
(120dB SPL, 15 ms broadband noise burst)
1
• The sum of monaural cues?
• Subjects: CBA/CaJ mice 3, 6, 12, 24 months old
• Mice held in acoustically transparent wire cage
mounted to a platform and accelerometer
C
40
% Inhibition
20
• None of the groups show significant
inhibition for the 7° swap
60
• 180° speaker swap has inhibitory effect
intermediate to noise offset and onset
(dashed grey curve shows simple average
of on- and offset data)
0
Methods
• Same design as Experiment 1, except
minimum angle is 7°
20
-20
% Inhibition
% Inhibition
• 180° speaker swap is significant from 5 to
300 ms, with a hint of facilitation at 1ms
180
90
45
22.5
15
60
What are the neural bases for age-related changes in spatial acuity in the mouse?
• 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
Previous behavioural measures of spatial acuity in the mouse
•19° in the 2 month old C57 mouse (Heffner, Koay, & Heffner, 2001)
24 month old (N=18)
0
% Inhibition
C
•Does a change in spatial location of a continuous sound source cause prepulse inhibition?
How do these parameters change with age?
40
Off (N=7), On (N=6), Swap (N=13)
•7-15° in 2 month old house mouse (Ehret & Dreyer, 1984)
6 month old (N=12)
Angular Shift : 180 
20
-20
• 6 month old mice (N=12)
12 month old (N=12)
0
•Startle response amplitude is modulated by prior perturbation of the acoustic environment (inhibition)
How does detection of a change in spatial location depend on stimulus duration?
60
Relative Inihibition (%)
% Inhibition
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
Is 180° speaker swap inhibitory?
100
Experiment 3: Frequency Effect on Speaker Swap
• 3 age groups:
Question 1:
% Inhibition
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
Experiment 2: Age Effect on Speaker Swap
Experiment 1: Broad Band Noise Speaker Swap
Relative Inihibition (%)
Introduction
15
22.5
45
90
Angular Separation (degrees)
180
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.
Supported by NIA Grant #AG09524 and The Schmitt Program on Integrative Brain Research