Download Auditory Neuron Responses to Predicted Synaptic Input Derived

Auditory Neuron Responses to Predicted Synaptic Input Derived from Cochlear Prosthetic Devices
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Maloney, Sean ; Oline, Stefan ; Brughera, Andrew ;Burger, R. Michael
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Department of Biology, Lehigh University 2Department of Biomedical Engineering, Center for Hearing Research, Boston University
ABSTRACT
METHODS
Binaural hearing enables multiple functions of the hearing system, including sound localization. In
the mammalian auditory circuitry, the first neurons responsible for comparing sound from the two
ears are found in the Medial Superior Olive (MSO). While there have been many studies on MSO
neuron physiology, details concerning how these neurons generate meaningful patterns of activity
in response to synaptic input are poorly understood. In this study, we used dynamic clamp to study
neurons from acute brain slices from Mongolian gerbils in vitro. Whole cell dynamic clamp provides
naturalistic synaptic input that neurons are predicted to receive in vivo. We simulated synaptic input
to MSO neurons evoked by acoustic stimuli at both 100 Hz (low frequency) and 1000 Hz (high
frequency). We found that with lower frequency stimuli, the cells respond significantly more at 180
degrees out of phase in comparison to 90 degrees out of phase. At the higher frequency, the
opposite is true (which is the situation in vivo.) We attempted to modulate this effect by changing
the strength of the synapse. Neither increasing nor decreasing the strength of each synapse
eliminated the out of phase spiking. We also changed the number of inputs per side, and while the
sample size is small, the data show a trend toward no effect on out of phase spiking. These results
suggest that inhibition may be required to process low frequencies compared to higher frequencies.
We speculate that this could be a result of the interaction between stimulus frequency and the
refractory period of the neuron. Future studies will include adding monaural (EEI) and binaural (EEII)
inhibition to the dynamic clamp protocols in order to observe the changes to the out of phase
stimuli.
Dynamic Clamp
Manipulating the number of synapse per side does not create a change in ITD response
Predicted synaptic input is
injected into cell
Computer program interprets
synaptic event profile
Neuron response is monitored
Event profile created based on specific
conditions predicted from cochlear implant
activity
Dynamic Clamp involves injecting current
directly into a neuron that mimics the
information that the cell would be receiving
from the synaptic inputs. These inputs are
synthesized computationally prior to injection.
Using this method we can manipulate many
factors that may influence efficient coding of
ITDs including: spike rate, synchrony value,
frequency, number of inputs, and length of
event. In the experiments shown the spike rate
was set to 250 spike/sec and the synchrony
value was set to 1 (in order to best mimic neural
inputs evoked in a cochlear implant patient.)
Identifying action potentials in an MSO neuron output trace
10 mV
100 ms
INTRODUCTION
Typical response for in phase stimuli
Narrowed window of typical response
Threshold is determined and the number of action potentials (denoted by arrows) above are counted.
The responses below threshold (a few have been denoted by triangles) are considered to be EPSPs
and are not counted.
RESULTS
The Medial Superior Olive (MSO) nucleus is
responsible for processing the ITD cue in
the mammalian auditory circuitry. The ITD
selectivity allows organisms to localize
sound on the horizontal plane for low
frequency sounds .
100 Hz
-270
1000 Hz
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1.2
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Normalized Number of Spikes
Coincidence detecting circuitry of the mammal
Excitation only creates sub-optimal ITD response for low frequency input
Normalized Number of Spikes
Interaural time differences are the acoustic cue animals use to localize low frequency stimuli. ITDs
arise from arrival time differences at the two ears that systematically vary with sound source
position in space. ITDs create frequency specific phase differences at the two ears. The second
order neurons that send excitatory information to the MSO provide a precisely timed “phase
locked” signal to the MSO. MSO neurons, in turn, vary their firing rate according to the degree to
Here we show that changing the number of inputs coming from each ear does not affect the out
of phase spiking during low frequency input. However for 1000 Hz, it appears that lower number
of inputs may narrow the tuning curve better at lower synaptic strength.
0.8
0.6
0.4
-180
0.6
0
0
90
180
270
-270
 Manipulating the strength of the synapse does not alleviate the out of phase “noise response”
0.4
0.2
0
 In a purely excitatory model (EE), MSO neurons have higher amounts of out of phase noise at
lower frequencies
0.8
0.2
-90
CONCLUSIONS
-180
-90
0
90
180
270
Phase (in degrees)
Phase (in degrees)
At this low frequency input, the response at 180
degrees (completely “out-of-phase”) is stronger
than at 90 degrees. This would create improper
signaling from the MSO neuron.
At this high frequency input, the response at 180
degrees is lower than 90 degrees. This is the
expected result as the synaptic inputs are not
strong enough to summate to action potential.
Changing the strength of the excitation does not impact the ITD response
100 Hz
16% Threshold
0.6
0.4
0.2
0.8
0.6
0.4
0.2
0
0
-270
-180
-90
0
-0.2
Phase (in degrees)
MSO neurons respond optimally to coincident input. When they receive “out-of-phase” input from
the ears, the synaptic input does not typically summate to action potential threshold.
 We plan to get a larger sample size for the changing number of inputs protocol
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Normalized Number of Spikes
Normalized Number of Spikes
0.8
90
180
270
FUTURE
1.2
20% Threshold
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”Phase-locked” inhibition may be more important during lower frequency signals than higher
frequency signals
1000 Hz
25% Threshold
1.2
 As the period of a phase in low frequency input is longer than in high frequency input, the out of
phase inputs may occur outside of the refractory time of the neuron (a period in which it is
difficult to cause spiking).
-270
-180
-90
0
90
180
270
-0.2
Phase (in degrees)
From this series of experiments (which had 4 inputs per ear), it is not clear if the strength of the
synapse correlates with a change in the out of phase response in the low frequency input. During the
high frequency input, there definitely does not seem to be any change.
We plan on adding
inhibition into the
protocol, which we
believe will alleviate
“out-of-phase”
responses