Article 2

Question 1

what does ITD stand for and what does it refer to?

Answer 1

interaural time differences. refers to the slight difference in the time in takes for sound to reach each of our ears. our brain uses these time differences to determine the direction or location of a sound source

Question 2

what does MSO stand for?

Answer 2

medial superior olive

Question 3

what does sensitivity to ITD’s require?

Answer 3

requires neuronal processing with a temporal acuity far beyond that normally observed in the mammalian CNS

Question 4

how has ITD processing been traditionally examined in mammals and birds?

Answer 4

is explained by means of a model devised by Jeffress more than 50 years ago.

Question 5

what does Jeffress model assume?

Answer 5

that the existence of arrays of coincidence-detector neurons receiving excitatory inputs from the two ears

Question 6

how do neurons in the Jeffress model respond maximally?

Answer 6

respond maximally when stimuli-evoked action potentials, phase-locked to the stimulus waveform, converge from each ear simultaneously

Question 7

what is the role of conduction delays in the Jeffress model?

Answer 7

Different conduction delays from each ear, assumed to result from a system of delay lines, provide a means by which different coincidence-detector neurons encode different ITDs.

Question 8

what does the systematic arrangement of delay lines in the Jeffress model create?

Answer 8

assumed to create a topographic representation of ITDs and a map of sound positions in the azimuthal plane

Question 9

what is the ITD-processing structure in birds?

Answer 9

is called the nucleus laminaris

Question 10

has the existence of a similar arrangement been confirmed for the mammal equivalent of the nucleus laminaris?

Answer 10

no, has not been directly confirmed for the MSO

Question 11

what is the mammalian equivalent of the nucleus laminaris?

Answer 11

MSO - medial superior olive

Question 12

what kind of input do spherical bushy cells from each cochlear nucleus provide to MSO neurons?

Answer 12

provide binaural excitatory input to MSO neurons

Question 13

where else do MSO neurons receive input form?

Answer 13

receive glycine-containing inputs directly onto their somata, arising from the medial, and lateral nucleus of the trapezoid body

Question 14

what was the goal of the study

Answer 14

to directly test the relevance of the jeffress model for the processing of ITD in mammals

Question 15

how did the study test the extent to which the jeffress model is relevant

Answer 15

recorded responses of ITD-sensitive neurons from the MSO of Mongolian gerbil

Question 16

how did they test the role of inhibition in the mammalian ITD detector?

Answer 16

used iontophoretic application of glycine and its antagonist strychnine

Question 17

how many responses were recorded?

Answer 17

36 low-frequency MSOs, 24 were binaurally excited

Question 18

how many were sensitive to ITDs

Answer 18

of the 24, 20 were

Question 19

what was the range of ITDs that were sensitive

Answer 19

30-85% change in discharge rate, which corresponds to the physiologically relevant range for gerbils (120 ms)

Question 20

what is the commonly held view of the jeffress model?

Answer 20

ITDs are systematically represented by individual coincidence-detector neurons, creating a place code of azimuthal position based on their max firing rates

Question 21

what did the study reveal about how MSO neurons respond to interauraly delayed tones?

Answer 21

MSO neurons respond maximally to interaurally delayed ‘best-frequency’ tones outside the physiologically relevant range
- peaks present outside of range

Question 22

where were ITD functions the steepest?

Answer 22

within the physiological range

Question 23

what relationship was observed between a neuron’s best frequency and the ITD that evokes the peak response?

Answer 23

Neurons with relatively low best frequencies respond maximally at relatively long ITDs, while neurons with relatively high best frequencies respond maximally at relatively short ITDs, with a slight scatter for neurons with best frequencies higher than 700 Hz.

Question 24

how does the map of best ITDs in the MSO appear to be organized?

Answer 24

run along the tonotopic gradient, suggesting that there is no ‘place map’ of ITDs within individual frequency channels in the MSO

Question 25

what else did researchers want to investigate

Answer 25

the glycinergic inhibitory input to the MSO

Question 26

how did they look at the role of this input on ITD coding?

Answer 26

glycine (inhibitory transmitter) or strychnine (its antagonist) was applied during recordings from MSO neurons

Question 27

what effect did glycine have?

Answer 27

almost completely abolished the response to the test tone in all 5 neurons, confirming their existence and inhibitory effect on MSO neurons

Question 28

what happened when strychine was applied to six neurons sensitive to ITDs?

Answer 28

Strychnine increased the discharge rate in all six neurons (by 50-86% at or close to zero ITD) and shifted the peak of the ITD functions towards zero ITD for the five neurons sensitive to ITDs.

Question 29

How did strychnine affect the ITD function of one of the neurons?

Answer 29

Initially, the neuron's peak ITD was +170 ms, outside the physiologically relevant range. With strychnine, the best ITD shifted downwards to +50 ms, reducing the dynamic range within the physiological range from 83% to 21%.

Question 30

What was the average shift in equivalent IPD for the five neurons after strychnine application?

Answer 30

The average shift was -0.127 cycles, indicating a significant change in ITD sensitivity (paired t-test, P < 0.014).

Question 31

What did the researchers do with the averaged IPD functions for the five neurons?

Answer 31

The researchers normalized each function to the maximum discharge rate in the presence of strychnine

Question 32

How much reduction in dynamic range did iontophoresis of strychnine produce on average?

Answer 32

Iontophoresis of strychnine, on average, produced a 67% reduction in the dynamic range of the response across the physiologically relevant range of ITDs.

Question 33

What is indicated by the yellow arrows in Fig. 3c?

Answer 33

The yellow arrows in Fig. 3c indicate the apparent effect of glycinergic inhibition, which varied at different ITDs. It was stronger when the ipsilateral stimulus was leading in time compared to when the contralateral stimulus was leading.

Question 34

Why is the observed influence of inhibition on ITD functions puzzling?

Answer 34

influence of inhibition on shifting the peaks of ITD functions is puzzling because glycinergic inputs to the MSO are insensitive to ITDs. The only explanation for this effect is that the inhibition occurs in specific phase relation to the excitatory inputs, meaning it is precisely phase-locked.

Question 35

What are the possible explanations for the influence of inhibition in shifting the peaks of ITD functions?

Answer 35

The possible explanations include ipsilaterally-driven inhibition that follows (phase lags) the ipsilateral excitation, contralateral inhibition that precedes contralateral excitation, or a combination of both. However, contralateral inhibition preceding contralateral excitation is a common phenomenon in the bat MSO, and contralateral inhibition has been shown to be more prominent than ipsilateral inhibition.

Question 36

How was the shift in ITD tuning resulting from phase-locked contralateral inhibition simulated?

Answer 36

The shift in ITD tuning due to phase-locked contralateral inhibition was simulated using a modified Hodgkin–Huxley model based on physiological findings in neurons of the anteroventral cochlear nucleus (AVCN).

Question 37

What specific properties of neurons in the AVCN were considered in the model?

Answer 37

The model incorporated properties such as nonlinear membrane properties, and it introduced an additional voltage-dependent, low-threshold potassium channel to make the single-compartment model sensitive to the relative timing of spike inputs.

Question 38

What effect did increasing the strength of timed inhibition have on the simulated ITD tuning?

Answer 38

Increasing the strength (conductance GI,max) of timed inhibition progressively shifted the central peak of the ITD tuning function towards longer values of ITD and reduced the overall discharge rate.

Question 39

How were the physiological results from the stimulation frequency of 1,000 Hz simulated in the model?

Answer 39

To simulate the physiological results at a stimulation frequency of 1,000 Hz, both the excitatory and inhibitory synaptic time constants were set to t = 0.1 ms, resulting in a half-time of 0.25 ms.

Question 40

What patterns were observed in the ITD functions for different stimulus frequencies in the model?

Answer 40

The ITD functions for various stimulus frequencies showed the typical pattern of a coincidence-detector neuron, with the position of the central peak being largely independent of stimulus frequency. However, there was a systematic tendency for the peak to shift toward lower ITDs as input level decreased, due to peripheral auditory filtering.

Question 41

What did the simulation results indicate about the role of phase-locked contralateral inhibition in neural responses?

Answer 41

The simulation results suggested that phase-locked and precisely timed contralateral inhibition, similar to what innervates the MSO from the MNTB, preceding contralateral excitation, can explain the observed neural responses.

Question 42

What is the main factor responsible for ITD tuning in the gerbil MSO?

Answer 42

ITD tuning in the gerbil MSO results from the interaction of precisely timed excitatory and inhibitory inputs.

Question 43

What role does glycinergic inhibition play in shaping ITD functions?

Answer 43

Glycinergic inhibition is responsible for tuning the steep slope of ITD functions to the physiologically relevant range by suppressing responses to ITDs where the ipsilateral stimulus leads in time.

Question 44

What is the likely source of the inhibitory input responsible for shaping ITD functions?

Answer 44

The most likely source of this inhibitory input is a monaural phase-locked inhibitory input, particularly from the contralateral medial nucleus of the trapezoid body (MNTB).

Question 45

What special features of the MNTB-derived inhibition are important for ITD processing?

Answer 45

The MNTB-derived inhibition has unique morphological and physiological features, including calyx synapses, which enable highly temporally precise transmission of neural signals. This contralateral inhibition must precede contralateral excitation to influence responses to negative ITDs.

Question 46

How does the temporal adjustment of the inhibitory time constant relate to the refinement of inputs in the MSO?

Answer 46

The fast time constant of inhibitory transmission may be related to the experience-dependent elimination of glycinergic synapses on MSO neurons, which occurs during the first days after hearing onset and refines inputs to MSO somata.

Question 47

What implications do these findings have for age-related hearing deficits?

Answer 47

The role of inhibitory transmitters in processing ITDs and evidence of age-related downregulation of inhibitory transmitters suggest new explanations for age-related hearing deficits, including difficulties in segregating sound sources.

Question 48

How do these results challenge the traditional model of low-frequency spatial hearing?

Answer 48

These results suggest that the traditional model of low-frequency spatial hearing, which focuses on the peaks of ITD functions, is inadequate. Instead, the slopes of ITD functions are considered critical for sound source localization in azimuth in the mammalian auditory system.