Age-Related Decrements in the Integrative Action of the Auditory Nervous System*
seen in the Acoustic Startle Reflex of the CBA Mouse
ARO 2003
#198
James R. Ison, Paul D. Allen, Jordan Bell, Catherine A. Moore, Carolyn M. Tyler
Brain & Cognitive Sciences, University of Rochester, Rochester, NY
RESULTS, Experiment 2
THE EXPERIMENT
RESULTS, Experiment 1
a) Acoustic Behavior - maximum summation with 2 ms gap for
1 ms tone pips in rats, then decay: Marsh et al. (1973) J.
Comp. Physiol. Psychol. 82:507-511.
Subjects: 35 CBA/6J mice were tested, at 6 weeks (n = 7: 4M,
3F); 7 months (n = 12: 5M, 7F); and 24 months of age (n = 16:
10 M, 6F). The mice were maintained with ad libitum food and
water in group cages. All procedures were approved as
following NIH Guidelines.
Seven month old mice responded most vigorously overall to
120 dB tone pips. Very old mice responded vigorously to single
pips but showed less summation to double pips than younger
mice. Relative ASR shows that the older mice had less temporal
integration and less peak summation but the longest summation
window. (Mean & SEM are shown.)
600
120 dB
b) CN electrical stimulation – maximum summation for .1 ms
shocks at 1-3 ms separation, then decay: Yeomans et al.
(1989) Brain Res. 486:147-158.
Apparatus and procedure: A photograph of the mouse in situ -
ASR (av-Units)
c) Explanation - Initial increased summation indicates
"decaying refractoriness" from S1 activation while later the
decline from peak summation indicates "decaying
excitation" adding to S2.
400
200
Mice received 110 (7 Mo) 120 (6 wk) or 130 dB (24 mo) tone
pips. The overall ASR levels were more similar here across
groups but again relative peak summation was weaker and
delayed in the oldest mice, and their summation window was
longer. (Mean & SEM are shown.)
6 wks. 120 dB
7 mo 110 dB
300
24 mo 130 dB
ASR (av-Units)
RESEARCH ON 2-PULSE SUMMATION IN ASR
200
100
PLAUSIBLE BASIS IN MEMBRANE BIOPHYSICS
Relative Response
C 0 1 2 3 4 5 6
b) The later decline in summation results as low-threshold K+
channels (such as Kv1) rectify baseline potential following
an EPSP, so that an S1 EPSP does not summate with an
S2 EPSP.
IMPLICATIONS FOR AGE EFFECTS ON
SUMMATION
5
4
6 wks.
7 mo.
24 mo.
3
2
1
0
C 0 1 2 3 4 5 6
10
Stimulus Onset Asynchrony (ms)
Old mice show less expression of both Kv3.1 and Kv1.1, thus**
The small test cage is mounted on an acrylic platform to
(a) following an AP, cell potentials should more slowly return to
baseline in old mice, retarding the growth of summation,
which an accelerometer is attached. The force of the reflexive
(**Inferred from Brew & Forsythe, 1995, J Neurosci, 15:18111822)
10
flinch to the overhead tone bursts (from TDT equipment) is
integrated for 100 ms following tone onset. 14 stimulus
At "C" a single pip is 120 dB; at "0" a single pip is 123 dB;
at "1" the 120 dB pip is 2 ms long. All groups show temporal
integration and summation, but old mice have more "jitter."
conditions were given on average 20 s apart, 11 trials per
condition in a semirandom order, with single tone pips, or
double pips separated by 0 to 9 ms gaps.
Work supported by NIA, AG09524, by the Schmitt Program on Integrative Brain Research,
and by NIDCD (CNCS) P30DC05409. The idea for this work grew out of conversations with
Helen Brew, Josh Gittelman, and Bruce Tempel in Seattle WA, April 2002 .
* With apologies to C.S. Sherrington
Relative Response
a) Initial increased summation results as high-threshold K+
channels (such as Kv3) rectify baseline potential following
the S1 AP, and thus permit a second response to S2
(b) but when an EPSP is present without an AP, then these
nerve fibers should more slowly return to baseline, this
resulting in an overall longer summation time.
0
0
C 0 1 2 3 4 5 6
10
C 0 1 2 3 4 5 6
10
3
2
1
0
Stimulus Onset Asynchrony (ms)
CONCLUSIONS
Old mice respond as vigorously as younger mice for brief
stimuli but show reduced peak summation for double pulses,
while their summation window is longer. These data are
consistent with the understanding that old mice express fewer
fast acting K+ channels that return membrane potentials to
baseline following a perturbation. This loss must diminish the
temporal precision of neural processing, which may be
expected to degrade sensory function in many auditory tasks.