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Perceptual odor adaptation
A technique for characterizing the time course of adaptation in mice
Olivia Munizza1  Wendy M Yoder2  Michelle Lyman1  Leslie Gaynor2,3  Barry Setlow2,4,6  Jennifer L Bizon3,4,5,6  David W Smith2,5
1Program in Interdisciplinary Studies, Neurobiological Sciences  2Program in Behavioral and Cognitive Neuroscience, Department of Psychology  3Department of English  4Department of Psychiatry  5Center for Smell and Taste  6Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida
5 5
Paradigm and behavioral methodology
Baseline thresholds are estimated first Time course of rapid adaptation│Humans
Acknowledgments
References
Time course of rapid adaptation │Mice
1. Albers M, Tabert M, Devanand D. 2006. Olfactory dysfunction as a predictor of neurodegenerative disease. Current Neurology and Neuroscience
Reports 6:379-389.
2. Bodyak N, Slotnick B. 1999. Performance of mice in an automated olfactometer: odor detection, discrimination and odor memory. Chemical Senses
24:637–645.
3. Kelliher K, Ziesmann J, Munger S, Reed R, Zufall F. 2003. Importance of the CNGA4 channel gene for odor discrimination and adaption in behaving
mice. PNAS 100:4299-4304.
4. Li W, Howard JD, Gottfried JA. 2010. Disruption of odour quality coding in piriform cortex mediates olfactory deficits in Alzheimer’s disease. Brain
133:2714-2726.
5. Smith D, Gamble K, Heil T. 2010. A novel psychophysical method for estimating the time course of olfactory rapid adaptation in humans. Chemical
Senses 35: 717-725.
6. Zufall F, Leinders-Zufall T. 2000. The cellular and molecular basis of odor adaptation. Chemical Senses 25: 473-481.
Much is
known about
the mechanisms
and temporal
characteristics
underlying odor
adaptation.
wendyyoder@ufl.edu
Figure 1: General Method. Licking in the
presence of the target odorant (S+) results
in 5 µl of liquid reinforcement (Ensure).
Conversely, incorrectly 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
Go No/Go Discrimination Task
1 block
20 pseudorandomized trials
Reinforcement
5-s Time-out
+
-
Figure 3: Stimulus conditions.
Baseline thresholds were estimated in
the presence of a null, adapting
background. Then adaptation was
measured by varying both time (onset
delays) and concentration: (AO=1x
threshold) and (AO=2x threshold).
Figure 3: Time course of adaptation, plotted as
changes in threshold at different adapting odorant
(AO) concentrations. A 2000-ms null stimulus (DH2O)
served as the AO in the baseline condition (black
circles). Mean detection thresholds are plotted for
thresholds measured alone and in the presence of the
AO. AO concentrations were set relative to each
animal’s threshold (1x threshold concentration, grey
squares; 2x threshold concentration, grey circles.
Asymptotic levels of adaptation were similar for both
concentrations, though the rate of adaptation was
faster for the 2x threshold AO condition.
Figure 5: Mean change in
threshold as a function of
AO concentration. Increases
in threshold stimulus
concentration were evident
even at 100-ms and
increased to an asymptotic
level of 100% (v/v) with
onset delays longer than
600-ms (solid line). Error
bars represent standard
deviations. Dashed lines
represent a fitted, two-
component sigmoidal curve
for the 1x AO concentration
and a fitted, two-component
exponential for the 2x AO
concentration.
Our laboratory has previously
shown that rapid odor adaptation
can be measured in human
subjects using a novel paradigm.
The present study extends
our technique to measure
the time course of
adaptation in mice.
Figure 4: Individual (n=4) baseline thresholds. Initial
thresholds were estimated in the presence of DH2O (as the
adapting odorant). Mice were tested in incremental steps
using serial dilutions. Threshold was defined as the lowest
concentration the mouse received ≥85% accuracy. The
odor sampling duration was gradually increased from 0 ms
to 1000 ms delays at threshold.
Figure 6: Time course of adaptation, plotted
as changes in threshold. To more directly
compare adaptation in humans and mice, the group
mean contour from the present study can be
compared with human psychophysical estimates
collected with the same odorant and simultaneous
odorant paradigm. For humans, measurable
differences in threshold were evident following a 50-
ms AO exposure, whereas observable differences in
mice were not evident until 100 or 200-ms. Although
the smaller group size (n=4 mice) could potentially
account for this disparity, systematic, adaptation-
induced threshold increases were routinely observed
for all mice. This suggests that while initial, baseline
thresholds may vary across mice (and humans), the
general adaptation trend remains relatively consistent.
Discussion and translational applications
This psychophysical paradigm can be
adapted in animal models, where
experimental and genetic manipulations
can be used to characterize the different
mechanisms underlying odor adaptation.
These data further establish a critical
temporal link between perceptual
adaptation and olfactory receptor
mechanisms at the periphery and set the
groundwork for future research seeking to
establish a link between olfactory adaptation
impairments and pathological progression
in certain neurodegenerative diseases.1
We thank Dr. Barry Ache, Center for
Smell and Taste, University of Florida,
for conference travel funding.
1
Our olfactory environments are
characterized by rapidly changing
chemical fluctuations.
Adaptation is a
complex, time
dependent process
that functions to
limit receptor
saturation.
It suppresses
neural responses
to sustained
stimulation and
enhances the
detection of new
chemical stimuli
But behavioral
measures are
still needed to
determine how
adaptation affects
perception.
Figure 2: Schematic presentation of odor adaptation. The
premise of this technique is that extended presentation of an
odorant will produce odor adaptation, decreasing the sensitivity of
the receptor and increasing thresholds for a brief, “simultaneous”
target odorant presented at different temporal points after the
adapting stimulus-onset.
1
2
3 4
5
6 7
8
9
10
11
12
13
14
15
16

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Adaptation_Poster

  • 1. Perceptual odor adaptation A technique for characterizing the time course of adaptation in mice Olivia Munizza1  Wendy M Yoder2  Michelle Lyman1  Leslie Gaynor2,3  Barry Setlow2,4,6  Jennifer L Bizon3,4,5,6  David W Smith2,5 1Program in Interdisciplinary Studies, Neurobiological Sciences  2Program in Behavioral and Cognitive Neuroscience, Department of Psychology  3Department of English  4Department of Psychiatry  5Center for Smell and Taste  6Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida 5 5 Paradigm and behavioral methodology Baseline thresholds are estimated first Time course of rapid adaptation│Humans Acknowledgments References Time course of rapid adaptation │Mice 1. Albers M, Tabert M, Devanand D. 2006. Olfactory dysfunction as a predictor of neurodegenerative disease. Current Neurology and Neuroscience Reports 6:379-389. 2. Bodyak N, Slotnick B. 1999. Performance of mice in an automated olfactometer: odor detection, discrimination and odor memory. Chemical Senses 24:637–645. 3. Kelliher K, Ziesmann J, Munger S, Reed R, Zufall F. 2003. Importance of the CNGA4 channel gene for odor discrimination and adaption in behaving mice. PNAS 100:4299-4304. 4. Li W, Howard JD, Gottfried JA. 2010. Disruption of odour quality coding in piriform cortex mediates olfactory deficits in Alzheimer’s disease. Brain 133:2714-2726. 5. Smith D, Gamble K, Heil T. 2010. A novel psychophysical method for estimating the time course of olfactory rapid adaptation in humans. Chemical Senses 35: 717-725. 6. Zufall F, Leinders-Zufall T. 2000. The cellular and molecular basis of odor adaptation. Chemical Senses 25: 473-481. Much is known about the mechanisms and temporal characteristics underlying odor adaptation. wendyyoder@ufl.edu Figure 1: General Method. Licking in the presence of the target odorant (S+) results in 5 µl of liquid reinforcement (Ensure). Conversely, incorrectly 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 Go No/Go Discrimination Task 1 block 20 pseudorandomized trials Reinforcement 5-s Time-out + - Figure 3: Stimulus conditions. Baseline thresholds were estimated in the presence of a null, adapting background. Then adaptation was measured by varying both time (onset delays) and concentration: (AO=1x threshold) and (AO=2x threshold). Figure 3: Time course of adaptation, plotted as changes in threshold at different adapting odorant (AO) concentrations. A 2000-ms null stimulus (DH2O) served as the AO in the baseline condition (black circles). Mean detection thresholds are plotted for thresholds measured alone and in the presence of the AO. AO concentrations were set relative to each animal’s threshold (1x threshold concentration, grey squares; 2x threshold concentration, grey circles. Asymptotic levels of adaptation were similar for both concentrations, though the rate of adaptation was faster for the 2x threshold AO condition. Figure 5: Mean change in threshold as a function of AO concentration. Increases in threshold stimulus concentration were evident even at 100-ms and increased to an asymptotic level of 100% (v/v) with onset delays longer than 600-ms (solid line). Error bars represent standard deviations. Dashed lines represent a fitted, two- component sigmoidal curve for the 1x AO concentration and a fitted, two-component exponential for the 2x AO concentration. Our laboratory has previously shown that rapid odor adaptation can be measured in human subjects using a novel paradigm. The present study extends our technique to measure the time course of adaptation in mice. Figure 4: Individual (n=4) baseline thresholds. Initial thresholds were estimated in the presence of DH2O (as the adapting odorant). Mice were tested in incremental steps using serial dilutions. Threshold was defined as the lowest concentration the mouse received ≥85% accuracy. The odor sampling duration was gradually increased from 0 ms to 1000 ms delays at threshold. Figure 6: Time course of adaptation, plotted as changes in threshold. To more directly compare adaptation in humans and mice, the group mean contour from the present study can be compared with human psychophysical estimates collected with the same odorant and simultaneous odorant paradigm. For humans, measurable differences in threshold were evident following a 50- ms AO exposure, whereas observable differences in mice were not evident until 100 or 200-ms. Although the smaller group size (n=4 mice) could potentially account for this disparity, systematic, adaptation- induced threshold increases were routinely observed for all mice. This suggests that while initial, baseline thresholds may vary across mice (and humans), the general adaptation trend remains relatively consistent. Discussion and translational applications This psychophysical paradigm can be adapted in animal models, where experimental and genetic manipulations can be used to characterize the different mechanisms underlying odor adaptation. These data further establish a critical temporal link between perceptual adaptation and olfactory receptor mechanisms at the periphery and set the groundwork for future research seeking to establish a link between olfactory adaptation impairments and pathological progression in certain neurodegenerative diseases.1 We thank Dr. Barry Ache, Center for Smell and Taste, University of Florida, for conference travel funding. 1 Our olfactory environments are characterized by rapidly changing chemical fluctuations. Adaptation is a complex, time dependent process that functions to limit receptor saturation. It suppresses neural responses to sustained stimulation and enhances the detection of new chemical stimuli But behavioral measures are still needed to determine how adaptation affects perception. Figure 2: Schematic presentation of odor adaptation. The premise of this technique is that extended presentation of an odorant will produce odor adaptation, decreasing the sensitivity of the receptor and increasing thresholds for a brief, “simultaneous” target odorant presented at different temporal points after the adapting stimulus-onset. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16