Transcript Symposium Poster - uospur

Gap Detection in Auditory Cortex Signaling
Ulysses Duckler, Mike Wehr, Aldis Weible, Lucas Ott
Institute of Neuroscience, University of Oregon Summer 2015 OURS
Abstract
Aims
Mouse Model
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Damage or degeneration to the auditory cortex due to aging impairs the faculties
of speech recognition and other structured auditory processing. Noise gaps are a
simple time dependent auditory signal that can be used to provide information on the
activity of the auditory cortex by measuring gap detection. The presence of small gaps
in white noise weakens the startle response in vertebrates, so gap detection can be
measured by response strength when a gap is paired with a loud noise, and
compared to the startle without the gap. The startle response is mediated by motor
neurons through a brainstem circuit in the auditory cortex that carries the temporal
auditory signal through layered neurons.
This research project with the Wehr lab will
investigate the mechanisms of auditory cortex signaling in mice using gap detection
testing, gathering data on gap detection in mice with layer five or layer four neuron
activity that can be optogenetically suppressed or enhanced. If this research shows
that layer five and layer four suppressed mice display significantly dissimilar gap
detection activity, it could suggest that the mechanics of auditory cortex signaling is
not as simple and linear as previously thought. The temporal mechanics of how
auditory stimuli is processed by the auditory cortex is fundamental to understanding
how degradation of the auditory cortex can lead to age-related deficiencies in speech
comprehension.
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Figure 4. Our mice setup for behavioral trials. The
startle amplitude in response to sound stimuli is
measured by the pressure plate underneath while the
mouse is held in place.
Use gap detection to measure temporal acuity while silencing layered cortical
interneurons to understand auditory cortex signaling pathways.
Test if the auditory cortex circuit mechanisms follow a serial model.
Figure 5. Noise gaps followed by a sound stimulus causes
prepulse inhibition so that the mouse startle response is lessened
when a burst of noise is preceded by a noise gap. The length of
the noise gap determines the percentage of startle attenuation .
Speech Processing
Figure 9. Our candidate circuit model of auditory cortex signaling pathways. Aim 1 is to test how the
comparison circuit operates and if signal flow is serial (L4->L2/3->L5/6)
Figure 6. Small noise gaps trigger a gap termination response auditory cortical neurons, which allows for
gap detection. Startle attenuation can be used as a measure of gap detection acuity.
Expirimental design
Optigenetic Tools
Behavioral trials with Nr5A and Gpr26
lines with ChR2 and Arch supression.
Figure 1. The difference in voice onset time when
discriminating between similar phonemes is an
example of temporally structured sound that is
processed by the auditory cortex.
Figure 2. Auditory cortex shutdown by laser activated
PV-ChR2 in mice impairs performance in phoneme
discrimination behavioral trials.
Gap Detection
Gap detection is mediated by the auditory cortex and can act as a means of
mesureing auditry cortext activity.
Figure 10. Validation of layer 4 and layer 5 specific mouse
lines respectively with retrogradely labeled Cre virus in
Inferior colliculus neurons.
Table 1. Table of alternative circuit models by layer
and the result of layer targeted suppression if the
serial model is refuted.
Future directions and acknowledgements
Figure 7. Cartoon diagram of optic fibre insertion
into the mouse auditory cortex.
Figure 3. Suppression of inhibitory PV+ or SOM+ cells with Arch enhances gap detection and
suppressing excitatory neurons with ChR2 has the opposite effect.
Figure 8. 2D section diagram of optic laser area of
effect on auditory cortex layers.
Optegetic techineques allow for more precise inhibition or activation of cortical
interneurons then drug or lesion studies. ChR2 and Arch are two tools for auditory cortext
shutdown.
This work was supported by NICHD Summer Research Program at the University of Oregon (NIH-1R25HD070817)
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High intensity lasers for absolute suppression of auditory cortex neurons.
Exploring NP39 (layer 2/3) mouse lines and how that layer fits into the circuit model.
Fear conditioning to enhance gap termination response in behavioral trials.
Reffrences
Weible, A.P., et al., Auditory Cortex is Required for Fear Potentiation of Gap Detection. J Neurosci, 2014. 34(46):
p. 15437-45.
Weible, A.P., et al., Perceptual Gap Detection is Mediated by Gap Termination Responces in Auditory Cortex.
Current Biology, in press.