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Functional refinement in the projection from ventral cochlear nucleus to lateral superior olive precedes hearing onset in rat.

Case DT, Zhao X, Gillespie DC - PLoS ONE (2011)

Bottom Line: Principal neurons of the lateral superior olive (LSO) compute the interaural intensity differences necessary for localizing high-frequency sounds.In the NMDAR-mediated response, GluN2B-containing NMDARs predominate in the first postnatal week and decline sharply thereafter.Our data are consistent with a model in which the excitatory and inhibitory projections to LSO are functionally refined in parallel during the first postnatal week, and they further suggest that GluN2B-containing NMDARs may mediate early refinement in the VCN-LSO pathway.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT
Principal neurons of the lateral superior olive (LSO) compute the interaural intensity differences necessary for localizing high-frequency sounds. To perform this computation, the LSO requires precisely tuned, converging excitatory and inhibitory inputs that are driven by the two ears and that are matched for stimulus frequency. In rodents, the inhibitory inputs, which arise from the medial nucleus of the trapezoid body (MNTB), undergo extensive functional refinement during the first postnatal week. Similar functional refinement of the ascending excitatory pathway, which arises in the anteroventral cochlear nucleus (AVCN), has been assumed but has not been well studied. Using whole-cell voltage clamp in acute brainstem slices of neonatal rats, we examined developmental changes in input strength and pre- and post-synaptic properties of the VCN-LSO pathway. A key question was whether functional refinement in one of the two major input pathways might precede and then guide refinement in the opposite pathway. We find that elimination and strengthening of VCN inputs to the LSO occurs over a similar period to that seen for the ascending inhibitory (MNTB-LSO) pathway. During this period, the fractional contribution provided by NMDA receptors (NMDARs) declines while the contribution from AMPA receptors (AMPARs) increases. In the NMDAR-mediated response, GluN2B-containing NMDARs predominate in the first postnatal week and decline sharply thereafter. Finally, the progressive decrease in paired-pulse depression between birth and hearing onset allows these synapses to follow progressively higher frequencies. Our data are consistent with a model in which the excitatory and inhibitory projections to LSO are functionally refined in parallel during the first postnatal week, and they further suggest that GluN2B-containing NMDARs may mediate early refinement in the VCN-LSO pathway.

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Representative input-output curves between P1 and P9.A: P2 cell: example individual traces and input-output curve in the VCN-LSO pathway. As shown here, input-output curves obtained for the youngest ages typically lacked clear steps. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. B: P5 cell: example individual traces and input-output curve. Stepwise increases in response amplitude could typically be distinguished at this age. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. C: P9 cell: example individual traces and input-output curve. Stepwise increases in current amplitude were nearly always distinguishable, with the number of steps rarely exceeding 3. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. D: Representative I/O-curve of P1 cell, showing average maximal response in plateau phase of 73.8±3.0 pA. In order to focus on the plateau phase, lower stimulation intensities were sparsely sampled in the youngest cells and thus the appearance of discrete steps in this example is an artifact of sparse sampling. E: Response amplitudes to minimal stimulation for the cell shown in D (mean minimal response of 18.3±0.9 pA). Black circles indicate “signal” responses whose shape matched an average minimal-response template; “noise” responses (gray) are shown for comparison.
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pone-0020756-g001: Representative input-output curves between P1 and P9.A: P2 cell: example individual traces and input-output curve in the VCN-LSO pathway. As shown here, input-output curves obtained for the youngest ages typically lacked clear steps. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. B: P5 cell: example individual traces and input-output curve. Stepwise increases in response amplitude could typically be distinguished at this age. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. C: P9 cell: example individual traces and input-output curve. Stepwise increases in current amplitude were nearly always distinguishable, with the number of steps rarely exceeding 3. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. D: Representative I/O-curve of P1 cell, showing average maximal response in plateau phase of 73.8±3.0 pA. In order to focus on the plateau phase, lower stimulation intensities were sparsely sampled in the youngest cells and thus the appearance of discrete steps in this example is an artifact of sparse sampling. E: Response amplitudes to minimal stimulation for the cell shown in D (mean minimal response of 18.3±0.9 pA). Black circles indicate “signal” responses whose shape matched an average minimal-response template; “noise” responses (gray) are shown for comparison.

Mentions: In order to understand whether and how input number and strength change before hearing onset in the VCN-LSO pathway, we recorded responses to stimuli of increasing amplitude in brainstem slices from animals P1-12 and then plotted input-output curves (I/O curves) of response amplitude as a function of stimulus amplitude for each neuron. In theory, at the weakest stimulation strengths no fibers are activated, whereas stimuli of increasing strength successively recruit additional fibers, the activation of which can be seen as discrete increases in response amplitude. We found that I/O-curves from the youngest slices differed qualitatively from those obtained from slices around hearing onset. As shown in the example figure, most of the I/O curves from slices younger than P3 rose smoothly with increasing stimulus intensity, as expected for neurons that receive many weak inputs (Fig. 1A). In most of the neurons from P4-5 slices, discrete steps were apparent in the I/O relationships (Fig. 1B), and by P9 most of the I/O-curves exhibited only 1–3 steps (Fig. 1C). As shown in these representative examples, some of the steps in response amplitude at P9 were as large as the maximal responses seen before P3 (Compare the P2 example, Fig. 1A, with average maximal amplitude 427.8±9.2 pA to the P9 example, Fig. 1C, with average step sizes 174.1±15.0 pA, 418.1±21.8 pA, 153.2±22.8 pA. Note different y-axis scales.). Thus, single fibers at the older ages were able to drive LSO neurons as strongly as did the entire projection in slices of the youngest ages. Because steps in response amplitude were rare in the I/O curves of the youngest cells, it was generally not possible to directly determine the number of inputs to a single LSO cell from the I/O curves alone. In order to estimate this number for the youngest ages, we divided the average maximal response obtained from the plateau phase of the I/O-curve (Fig. 1D) by the mean observable single-fiber strength obtained from minimal stimulation (Fig. 1E) (for this P1 example cell, average maximal response = 73.8±3.0 pA and average minimal response = 18.3±0.9 pA; therefore, estimated #inputs = 4). For these youngest cells, responses were sparsely sampled at the lower stimulus intensities in order to focus on the plateau phase; thus, the appearance of steps in this example is a sampling artifact.


Functional refinement in the projection from ventral cochlear nucleus to lateral superior olive precedes hearing onset in rat.

Case DT, Zhao X, Gillespie DC - PLoS ONE (2011)

Representative input-output curves between P1 and P9.A: P2 cell: example individual traces and input-output curve in the VCN-LSO pathway. As shown here, input-output curves obtained for the youngest ages typically lacked clear steps. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. B: P5 cell: example individual traces and input-output curve. Stepwise increases in response amplitude could typically be distinguished at this age. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. C: P9 cell: example individual traces and input-output curve. Stepwise increases in current amplitude were nearly always distinguishable, with the number of steps rarely exceeding 3. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. D: Representative I/O-curve of P1 cell, showing average maximal response in plateau phase of 73.8±3.0 pA. In order to focus on the plateau phase, lower stimulation intensities were sparsely sampled in the youngest cells and thus the appearance of discrete steps in this example is an artifact of sparse sampling. E: Response amplitudes to minimal stimulation for the cell shown in D (mean minimal response of 18.3±0.9 pA). Black circles indicate “signal” responses whose shape matched an average minimal-response template; “noise” responses (gray) are shown for comparison.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3111428&req=5

pone-0020756-g001: Representative input-output curves between P1 and P9.A: P2 cell: example individual traces and input-output curve in the VCN-LSO pathway. As shown here, input-output curves obtained for the youngest ages typically lacked clear steps. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. B: P5 cell: example individual traces and input-output curve. Stepwise increases in response amplitude could typically be distinguished at this age. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. C: P9 cell: example individual traces and input-output curve. Stepwise increases in current amplitude were nearly always distinguishable, with the number of steps rarely exceeding 3. Higher stimulus amplitudes elicited no increase in response size, and have been removed for clarity. D: Representative I/O-curve of P1 cell, showing average maximal response in plateau phase of 73.8±3.0 pA. In order to focus on the plateau phase, lower stimulation intensities were sparsely sampled in the youngest cells and thus the appearance of discrete steps in this example is an artifact of sparse sampling. E: Response amplitudes to minimal stimulation for the cell shown in D (mean minimal response of 18.3±0.9 pA). Black circles indicate “signal” responses whose shape matched an average minimal-response template; “noise” responses (gray) are shown for comparison.
Mentions: In order to understand whether and how input number and strength change before hearing onset in the VCN-LSO pathway, we recorded responses to stimuli of increasing amplitude in brainstem slices from animals P1-12 and then plotted input-output curves (I/O curves) of response amplitude as a function of stimulus amplitude for each neuron. In theory, at the weakest stimulation strengths no fibers are activated, whereas stimuli of increasing strength successively recruit additional fibers, the activation of which can be seen as discrete increases in response amplitude. We found that I/O-curves from the youngest slices differed qualitatively from those obtained from slices around hearing onset. As shown in the example figure, most of the I/O curves from slices younger than P3 rose smoothly with increasing stimulus intensity, as expected for neurons that receive many weak inputs (Fig. 1A). In most of the neurons from P4-5 slices, discrete steps were apparent in the I/O relationships (Fig. 1B), and by P9 most of the I/O-curves exhibited only 1–3 steps (Fig. 1C). As shown in these representative examples, some of the steps in response amplitude at P9 were as large as the maximal responses seen before P3 (Compare the P2 example, Fig. 1A, with average maximal amplitude 427.8±9.2 pA to the P9 example, Fig. 1C, with average step sizes 174.1±15.0 pA, 418.1±21.8 pA, 153.2±22.8 pA. Note different y-axis scales.). Thus, single fibers at the older ages were able to drive LSO neurons as strongly as did the entire projection in slices of the youngest ages. Because steps in response amplitude were rare in the I/O curves of the youngest cells, it was generally not possible to directly determine the number of inputs to a single LSO cell from the I/O curves alone. In order to estimate this number for the youngest ages, we divided the average maximal response obtained from the plateau phase of the I/O-curve (Fig. 1D) by the mean observable single-fiber strength obtained from minimal stimulation (Fig. 1E) (for this P1 example cell, average maximal response = 73.8±3.0 pA and average minimal response = 18.3±0.9 pA; therefore, estimated #inputs = 4). For these youngest cells, responses were sparsely sampled at the lower stimulus intensities in order to focus on the plateau phase; thus, the appearance of steps in this example is a sampling artifact.

Bottom Line: Principal neurons of the lateral superior olive (LSO) compute the interaural intensity differences necessary for localizing high-frequency sounds.In the NMDAR-mediated response, GluN2B-containing NMDARs predominate in the first postnatal week and decline sharply thereafter.Our data are consistent with a model in which the excitatory and inhibitory projections to LSO are functionally refined in parallel during the first postnatal week, and they further suggest that GluN2B-containing NMDARs may mediate early refinement in the VCN-LSO pathway.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Graduate Program, McMaster University, Hamilton, Ontario, Canada.

ABSTRACT
Principal neurons of the lateral superior olive (LSO) compute the interaural intensity differences necessary for localizing high-frequency sounds. To perform this computation, the LSO requires precisely tuned, converging excitatory and inhibitory inputs that are driven by the two ears and that are matched for stimulus frequency. In rodents, the inhibitory inputs, which arise from the medial nucleus of the trapezoid body (MNTB), undergo extensive functional refinement during the first postnatal week. Similar functional refinement of the ascending excitatory pathway, which arises in the anteroventral cochlear nucleus (AVCN), has been assumed but has not been well studied. Using whole-cell voltage clamp in acute brainstem slices of neonatal rats, we examined developmental changes in input strength and pre- and post-synaptic properties of the VCN-LSO pathway. A key question was whether functional refinement in one of the two major input pathways might precede and then guide refinement in the opposite pathway. We find that elimination and strengthening of VCN inputs to the LSO occurs over a similar period to that seen for the ascending inhibitory (MNTB-LSO) pathway. During this period, the fractional contribution provided by NMDA receptors (NMDARs) declines while the contribution from AMPA receptors (AMPARs) increases. In the NMDAR-mediated response, GluN2B-containing NMDARs predominate in the first postnatal week and decline sharply thereafter. Finally, the progressive decrease in paired-pulse depression between birth and hearing onset allows these synapses to follow progressively higher frequencies. Our data are consistent with a model in which the excitatory and inhibitory projections to LSO are functionally refined in parallel during the first postnatal week, and they further suggest that GluN2B-containing NMDARs may mediate early refinement in the VCN-LSO pathway.

Show MeSH
Related in: MedlinePlus