Background and significance
Interaction between age and perceptual difficulty in olfactory discrimination learning in F344 rats: relationships with spatial learning
Wendy M Yoder1 Leslie Gaynor2 Sarah N Burke5 Brandi K Ormerod5 Barry Setlow1,3,5 Jennifer L Bizon1,4,5 David W Smith1,5
1Program in Behavioral and Cognitive Neuroscience, Department of Psychology 2Program in Interdisciplinary Studies, Neurobiological Sciences 3Department of Psychiatry 4Center for Smell and Taste 5Department of Neuroscience, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida
Accuracy decreases as ∆carbon atoms decreases A subset of aged rats show spatial memory declines
Aging is a complex process and a
key risk factor for cognitive and
neural dysfunction, but declines are
rapid without early intervention.
Researchers are scrambling to
identify reliable biomarkers.
Fischer 344 rats may be an important
piece of the puzzle. As these rats
age, some show cognitive declines
that correlate with olfactory deficits.
Olfactory changes could predict
memory impairments, but first...
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Less overlap: Less Confusing
More overlap: More Confusing
Figure 2: Glomerular Activation Patterns Predict Olfactory Perception. Degree of glomerular overlap affects
perceptual similarity (i.e., tendency to confuse odorants). (A) Olfactory bulb activation patterns for the aliphatic
alcohols 1-propanol and 1-octanol (a difference of 5 carbon atoms). (B) Activation patterns for 1-heptanol and 1-
hexanol (a difference of 1 carbon atom). Glomerular Response Activity Archive: http://gara.bio.uci.edu
Figure 4. Homologous Series Tested. Three
functional groups were tested (aliphatic alcohols,
aliphatic aldehydes, aliphatic acids) to create 9
novel odorant pairs differing between one and five
carbon atoms. Odorant concentration was 1 ppm.
Three structurally unrelated controls were also
Stimuli: Aliphatic Functional Groups
We must increase
predictive validity by
acuity across a
continuum. This may
be achieved by
Figure 1: Model of olfactory perceptual similarity. Analogous to continuums in other
sensory systems, carbon chain length can be used as a gradient of generalization3,5,7.
In odor-guided discrimination paradigms, structurally similar odorants are more difficult
to distinguish and therefore, more perceptually confusing.
N F D
Z X T P
F T D Z U
H T P N F D
5 Carbon Difference
4 Carbon Difference
3 Carbon Difference
2 Carbon Difference
1 Carbon Difference
10 blocks total (20 trials each)
200 pseudorandomized trials
Fischer 344 Rats
Figure 3: General
Method. Licking in the
presence of the target
odorant (S+) results in
5 µl of liquid
licking in the presence
of the control odorant
(S-) results in a 5
second time-out; the rat
cannot initiate new trials
during this interval.4
Figure 5. Accuracy collapsed across
ΔC pairs. The accuracy in
discrimination performance decreased
in both young and aged rats as a
function of perceptual similarity
between the odorants in each pair.
Notably, however, across odor classes,
there was a significant Age X
Perceptual Similarity interaction, such
that aged rats performed
disproportionately less accurately on
more perceptually-similar problems.
Subsequent analyses compared
olfactory performance relative to spatial
learning performance in the water
maze. Notably, aged rats with good
water maze performance performed
comparably to young rats on the
olfactory discrimination problems
whereas aged rats with poor water
maze performance showed significant
impairments on the olfactory
discrimination problems relative to
young, particularly on the problems that
involved perceptually similar odorants.
Funding for this research was provided by NIH R01
AG024671 and the McKnight Brain Research Foundation..
Figure 8. Individual differences in spatial reference
memory performance among aged F344 rats, compared
with olfactory discrimination learning (Δ1). Together,
these findings suggest that a decreased ability to encode
perceptual distinctions may contribute to impaired stimulus
representations and cognitive impairments in aging.
Ongoing studies will test the hypothesis that both olfactory
and spatial learning deficits in a subset of aged rats are
associated with impaired spatial pattern separation.
Morris Water Maze: a well-characterized
task used to evaluate hippocampal-
dependent, spatial memory – a sensitive
measure of age-related, cognitive decline.
Discussion and translational applications
Is olfactory dysfunction
a promising behavioral
This measure could be
included in a battery with
other olfactory tests.
Importantly, our laboratory has expertise
assessing olfactory acuity in both
humans subjects and animal models.
Carbon chain length is one
critical determinant of
tasks should consider the
role of chemical structure.
The discrimination measure
described here may be
particularly useful for
alterations. Varying the
level of difficulty may
capture subtle deviations.
Although we know a correlation exists between age-related
cognitive decline and olfactory changes, we need to determine
which odor-guided tasks will be the most efficacious for
predicting onset and progression of memory deficits.
Figure 6. Accuracy across blocks for young and aged rats; ∆1 discriminations. Block data show performance
as a function of learning on more difficult discriminations. As a group, young rats perform better overall. As a group,
aged rats require additional training to perform on par with young. As noted above, however, this effect is driven
primary by a subset of aged rats.
Figure 7. Accuracy across blocks for young and aged rats; ∆5 discriminations. For both aged and young
rats, easier discriminations display minimal differences between groups.