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Transcript
Stereo-olfaction in Mouse Olfactory Navigation
PATRICK BROWN
University of Oregon (Smear Lab)
Stereo-olfaction is a sensory process, wherein
inputs from left and right olfactory sensory
neurons (OSNs) are compared in order to sense
the direction of an odor gradient1. In this project,
we are studying how stereo-olfactory signals are
neurally encoded. Odorant stimuli are difficult to
control, so we are using optogenetics to
investigate this process. Using optogenetics, we
can precisely control the timing and amplitude of
activity in the glomeruli, in which OSNs form
synapses with neurons of the olfactory bulb. Thus,
we can ask whether mice can perceive bilateral
differences in timing and amplitude2.
Background
• Odorant ligands bind to odorant receptors
expressed by OSNs.
• OSNs that express the same odorant receptor
project to a single glomerulus, where they
synapse with mitral and tufted cells, which
project axons to the cortex.
• The glomeruli are arranged spatially in a
stereotyped manner, forming identical maps in
the left and right olfactory bulbs. Thus, each
type of glomerulus is present on the two sides.
• Mitral and tufted cells project to the anterior
olfactory nucleus in a topographic manner;
neurons in the nucleus synapse near the
corresponding contralateral glomerulus.
A precise circuit links the left and
right olfactory bulbs.
Methods
We use a transgenic mouse that expresses
ChannelRhodopsin-2 in M72-expressing OSNs.
https://www.face
book.com/topic/
Behavioral
paradigm
ClaireKittrell/2876046
34763485?sourc
e=whfrt&position
=2&trqid=63146
4282020860343
4
Trial structure
SurgeryRecoveryHandlingWater
RestrictionLick TrainingPinene
DetectionLeft Laser DetectionRight
Laser DetectionRight=Go/Left=NoGo
Bilateral Timing Difference or Bilateral
Amplitude Difference
Mice are trained to lick when the left stimulus
precedes the right by 100ms, and to not lick when
the right stimulus precedes the left. We will
incrementally reduce the gap between the bilateral
stimuli, in order to determine their acuity for timing
differences. Similarly, simultaneous stimuli will be
presented with differences in amplitude in order to
isolate sensitivity to bilateral differences in neural
activity3.
The bilateral stimuli
are presented
immediately
following inhalation
to ensure that they
occur within the
same sniff,
simulating odorevoked activity.
Conclusions
This work suggests that timing cues at the
glomerular level are sufficient for stereoolfactory discrimination
Future directions
• Mice can differentiate between unilateral stimuli
presented at different times in the sniff; we
need to control for the possibility that they are
identifying lick and no-lick trials in this way4.
Therefore, it will be necessary to randomize the
time position of the stimulus relative to sniffing.
Results
Stimulation of these neurons with blue light evokes
neuronal activity, as would the M72 receptor’s odor
ligands.
Thus far, we have tested two mice in the stereotiming task, where they discriminate between leftthen-right and right-then-left stimuli. One of those
mice has consistently demonstrated the ability to
discriminate between left-first and right-first stimuli
with a 100ms timing gap. This mouse has also
performed above chance (greater than 50%) for a
50ms timing gap.
•
https://www.face
book.com/topic/
Learning Curve for Stereo-olfactory
Discrimination
Task
ClaireKittrell/2876046
34763485?sourc
e=whfrt&position
=2&trqid=63146
4282020860343
Acknowledgements
4
90
80
Percent Trials Correct
Introduction
Training sequence
70
.We
will reduce the timing gap in order to
determine the acuity of mice to timing cues.
• We will also investigate their sensitivity to
bilateral differences in amplitude, and
determine if amplitude differences are sufficient
for stereo-olfaction.
• Finally, we will determine the relationship
between amplitude and timing differences. We
hypothesize that presenting stimuli that differ in
both timing and amplitude will improve the
accuracy of stereo-olfactory discrimination.
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40
References
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Session
This research was funded by the NICHD Summer
Research Program at the University of Oregon
(NIH-R25HD070817). Additional thanks to Dr.
Matthew Smear, Dr. Roma Shusterman, Rachael
Alionhart, Teresa Findley, Kassina Kim-Hayes, and
Rosanna Borsoni.
16
1. Rajan, R., Clement, J. P. & Bhalla, U. S. Rats
smell in stereo. Science 311, 666–670 (2006).
2. Smear, M., Resulaj, A., Zhang, J., Bozza, T. &
Rinberg, D. Multiple perceptible signals from a
single olfactory glomerulus. Nature Publishing
Group 16, 1687–1691 (2013).
3. Smear, M. C. Beyond localization of function:
dissecting a neural code with optogenetics in New
Techniques in Systems Neuroscience 271–292
(Springer International Publishing, 2015).
doi:10.1007/978-3-319-12913-6_10
4. Smear, M., Shusterman, R., O’connor, R.,
Bozza, T. & Rinberg, D. Perception of sniff phase
in mouse olfaction. Nature 479, 397–400 (2011).