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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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Related in: MedlinePlus

Fractional current mediated by AMPARs increases between birth and hearing onset.A: Representative mixed glutamatergic responses from P1, P5 and P9 neurons (average of 10 recordings), scaled to peak AMPA current; distinct AMPA and NMDA components visible in each trace. B: Same traces as in A, showing the mixed glutamatergic current, the pharmacologically isolated NMDAR component, and the response after application of AMPAR and NMDAR antagonists, D-APV and CNQX, which abolishes the glutamatergic response. All recordings in Mg++-free ACSF. Note change in scalebars for P9 recordings. C: Ratios of peak AMPA/NMDA current in 39 cells from slices P1-P12. During this period, AMPA/NMDA ratio increases as a function of age (p = 0.012, Kruskal-Wallis; P1/2 vs P9/10, p = 0.048; P7/8 vs P9/10, p = 0.30; P9/10 vs P11/12 p = 0.010; linear regression slope 0.14/day, r2 = 0.32; exponential fit r2 = 0.36). Filled black circles represent means ± SEMs at two-day intervals. Filled gray circles represent cells shown in A,B. D: Increase in AMPA/NMDA ratio with age is accompanied by small increases in average AMPA current (open circles, regressed to gray line) and decreases in average NMDAR current (filled circles, regressed to black line).
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pone-0020756-g003: Fractional current mediated by AMPARs increases between birth and hearing onset.A: Representative mixed glutamatergic responses from P1, P5 and P9 neurons (average of 10 recordings), scaled to peak AMPA current; distinct AMPA and NMDA components visible in each trace. B: Same traces as in A, showing the mixed glutamatergic current, the pharmacologically isolated NMDAR component, and the response after application of AMPAR and NMDAR antagonists, D-APV and CNQX, which abolishes the glutamatergic response. All recordings in Mg++-free ACSF. Note change in scalebars for P9 recordings. C: Ratios of peak AMPA/NMDA current in 39 cells from slices P1-P12. During this period, AMPA/NMDA ratio increases as a function of age (p = 0.012, Kruskal-Wallis; P1/2 vs P9/10, p = 0.048; P7/8 vs P9/10, p = 0.30; P9/10 vs P11/12 p = 0.010; linear regression slope 0.14/day, r2 = 0.32; exponential fit r2 = 0.36). Filled black circles represent means ± SEMs at two-day intervals. Filled gray circles represent cells shown in A,B. D: Increase in AMPA/NMDA ratio with age is accompanied by small increases in average AMPA current (open circles, regressed to gray line) and decreases in average NMDAR current (filled circles, regressed to black line).

Mentions: Increases in synaptic strength at many glutamatergic synapses result from the insertion of AMPARs in the postsynaptic membrane, which can be seen as an increase in the ratio of AMPAR/NMDAR peak current [29]. Thus, we examined the relative contribution of NMDARs and AMPARs to stimulation in the VCN-LSO pathway before hearing onset. To minimize possible confounds from incomplete space clamp in these large cells and potential underestimation of NMDAR currents, these experiments were performed in Mg++-free ACSF. Clearly visible in all recordings before the addition of receptor subtype-specific antagonists (Fig. 3A, top) were an early, fast AMPAR-mediated peak and a later, more slowly decaying NMDAR-mediated peak. Shown in Figure 3B, for the cells in Figure 3A, are the pharmacologically isolated NMDAR components from which fractional contributions to peak current were measured. Because the mixed current at all ages was carried solely by AMPA and NMDA receptors, the AMPAR contribution could be calculated by subtracting the NMDAR-mediated current from the mixed glutamatergic current. These values were used to compute the AMPA/NMDA ratio, which increased as a function of age during the postnatal period before hearing onset (Fig 3C). In the youngest cells, NMDARs contributed a larger share to the EPSC than did AMPARs, whereas by hearing onset AMPARs contributed almost three times as much current as NMDARs. (AMPA/NMDA peak current ratio P1-P2, 0.72±0.11, n = 6; P3-P4, 0.97±0.23, n = 8; P5-P6, 1.24±0.25, n = 7; P7-P8, 1.03±0.15, n = 6; P9-P10, 1.35±0.20, n = 7; P11-12, 2.77±0.43, n = 5). This increase in the AMPA/NMDA ratio could be due to an addition of AMPARs or to a loss of NMDARs or both; linear regression for each current amplitude as function of age (Fig. 3D) offered weak support for an increase in size of the AMPAR-mediated response (slope 9.9 pA/day, r2 0.10), accompanied by a decrease in size of the NMDAR-mediated response (slope-7.5 pA/day, r2 0.072).


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)

Fractional current mediated by AMPARs increases between birth and hearing onset.A: Representative mixed glutamatergic responses from P1, P5 and P9 neurons (average of 10 recordings), scaled to peak AMPA current; distinct AMPA and NMDA components visible in each trace. B: Same traces as in A, showing the mixed glutamatergic current, the pharmacologically isolated NMDAR component, and the response after application of AMPAR and NMDAR antagonists, D-APV and CNQX, which abolishes the glutamatergic response. All recordings in Mg++-free ACSF. Note change in scalebars for P9 recordings. C: Ratios of peak AMPA/NMDA current in 39 cells from slices P1-P12. During this period, AMPA/NMDA ratio increases as a function of age (p = 0.012, Kruskal-Wallis; P1/2 vs P9/10, p = 0.048; P7/8 vs P9/10, p = 0.30; P9/10 vs P11/12 p = 0.010; linear regression slope 0.14/day, r2 = 0.32; exponential fit r2 = 0.36). Filled black circles represent means ± SEMs at two-day intervals. Filled gray circles represent cells shown in A,B. D: Increase in AMPA/NMDA ratio with age is accompanied by small increases in average AMPA current (open circles, regressed to gray line) and decreases in average NMDAR current (filled circles, regressed to black line).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3111428&req=5

pone-0020756-g003: Fractional current mediated by AMPARs increases between birth and hearing onset.A: Representative mixed glutamatergic responses from P1, P5 and P9 neurons (average of 10 recordings), scaled to peak AMPA current; distinct AMPA and NMDA components visible in each trace. B: Same traces as in A, showing the mixed glutamatergic current, the pharmacologically isolated NMDAR component, and the response after application of AMPAR and NMDAR antagonists, D-APV and CNQX, which abolishes the glutamatergic response. All recordings in Mg++-free ACSF. Note change in scalebars for P9 recordings. C: Ratios of peak AMPA/NMDA current in 39 cells from slices P1-P12. During this period, AMPA/NMDA ratio increases as a function of age (p = 0.012, Kruskal-Wallis; P1/2 vs P9/10, p = 0.048; P7/8 vs P9/10, p = 0.30; P9/10 vs P11/12 p = 0.010; linear regression slope 0.14/day, r2 = 0.32; exponential fit r2 = 0.36). Filled black circles represent means ± SEMs at two-day intervals. Filled gray circles represent cells shown in A,B. D: Increase in AMPA/NMDA ratio with age is accompanied by small increases in average AMPA current (open circles, regressed to gray line) and decreases in average NMDAR current (filled circles, regressed to black line).
Mentions: Increases in synaptic strength at many glutamatergic synapses result from the insertion of AMPARs in the postsynaptic membrane, which can be seen as an increase in the ratio of AMPAR/NMDAR peak current [29]. Thus, we examined the relative contribution of NMDARs and AMPARs to stimulation in the VCN-LSO pathway before hearing onset. To minimize possible confounds from incomplete space clamp in these large cells and potential underestimation of NMDAR currents, these experiments were performed in Mg++-free ACSF. Clearly visible in all recordings before the addition of receptor subtype-specific antagonists (Fig. 3A, top) were an early, fast AMPAR-mediated peak and a later, more slowly decaying NMDAR-mediated peak. Shown in Figure 3B, for the cells in Figure 3A, are the pharmacologically isolated NMDAR components from which fractional contributions to peak current were measured. Because the mixed current at all ages was carried solely by AMPA and NMDA receptors, the AMPAR contribution could be calculated by subtracting the NMDAR-mediated current from the mixed glutamatergic current. These values were used to compute the AMPA/NMDA ratio, which increased as a function of age during the postnatal period before hearing onset (Fig 3C). In the youngest cells, NMDARs contributed a larger share to the EPSC than did AMPARs, whereas by hearing onset AMPARs contributed almost three times as much current as NMDARs. (AMPA/NMDA peak current ratio P1-P2, 0.72±0.11, n = 6; P3-P4, 0.97±0.23, n = 8; P5-P6, 1.24±0.25, n = 7; P7-P8, 1.03±0.15, n = 6; P9-P10, 1.35±0.20, n = 7; P11-12, 2.77±0.43, n = 5). This increase in the AMPA/NMDA ratio could be due to an addition of AMPARs or to a loss of NMDARs or both; linear regression for each current amplitude as function of age (Fig. 3D) offered weak support for an increase in size of the AMPAR-mediated response (slope 9.9 pA/day, r2 0.10), accompanied by a decrease in size of the NMDAR-mediated response (slope-7.5 pA/day, r2 0.072).

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