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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

Paired-pulse depression decreases between birth and hearing onset.A: Representative responses to 50 Hz pulse-trains in P2, P5, and P9 cells; responses to the first five pulses only are shown. Greater paired-pulse depression between pulse 1 and 2 is evident in the youngest cell than in the older cells. B: Average responses to 10-pulse trains at four frequencies. At stimulation frequencies of 20 Hz or less, few differences are seen between ages. At 50 and 100 Hz, clear differences are obvious between age groups, and only the oldest (P9-12) cells are able to follow 100 Hz trains. C: Group data from B, showing paired-pulse ratios as pulse 2/pulse 1. At 10 and 20 Hz, age differences are not significant at the p<0.05 level (p = 0.48 and p = 0.063, one-way ANOVA). At 50 Hz, significant age differences are seen in paired-pulse depression (one-way ANOVA:  = 3.3*10−5), with greater depression in P1-2 slices than in P3-4 slices (posthoc Mann-Whitney p = 0.014) and in P5-8 slices than in P9-12 slices (p = 0.041). At 100 Hz, significant age differences are also seen (one-way ANOVA p = 0.071), with paired-pulse depression greater in P1-2 (p = 0.0018) and P3-4 slices than in P9-12 slices (p = 0.012).
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pone-0020756-g006: Paired-pulse depression decreases between birth and hearing onset.A: Representative responses to 50 Hz pulse-trains in P2, P5, and P9 cells; responses to the first five pulses only are shown. Greater paired-pulse depression between pulse 1 and 2 is evident in the youngest cell than in the older cells. B: Average responses to 10-pulse trains at four frequencies. At stimulation frequencies of 20 Hz or less, few differences are seen between ages. At 50 and 100 Hz, clear differences are obvious between age groups, and only the oldest (P9-12) cells are able to follow 100 Hz trains. C: Group data from B, showing paired-pulse ratios as pulse 2/pulse 1. At 10 and 20 Hz, age differences are not significant at the p<0.05 level (p = 0.48 and p = 0.063, one-way ANOVA). At 50 Hz, significant age differences are seen in paired-pulse depression (one-way ANOVA:  = 3.3*10−5), with greater depression in P1-2 slices than in P3-4 slices (posthoc Mann-Whitney p = 0.014) and in P5-8 slices than in P9-12 slices (p = 0.041). At 100 Hz, significant age differences are also seen (one-way ANOVA p = 0.071), with paired-pulse depression greater in P1-2 (p = 0.0018) and P3-4 slices than in P9-12 slices (p = 0.012).

Mentions: Circuits in the auditory brainstem are capable of supporting among the fastest firing rates in the nervous system. Additionally, varying patterns of activity in the mouse VCN-LSO pathway have been shown to differentially activate different glutamate receptor subtypes and different calcium sources [28]. To determine the capability of VCN-LSO synapses to support repetitive activity in the developing circuit, we added cyclothiazide to the perfusate to prevent AMPAR desensitization and measured responses to 50 Hz pulse-train stimuli delivered to the ventral acoustic stria. As judged by paired-pulse depression (PPD), neurons in the youngest slices were unable to follow at 50 Hz, a relatively slow frequency for the auditory brainstem (Fig. 6A). In order to ask how frequency-following matures between P1 and P12 we delivered pulse trains of 10 stimuli at 10, 20, 50, and 100 Hz to VCN-LSO fibers. Stimulation at lower frequencies (10 and 20 Hz, or 100 and 50 ms inter-stimulus intervals) yielded similar response profiles at all ages (Fig. 6B), whereas stimulation at higher frequencies (50 and 100 Hz, or 20 and 10 ms inter-stimulus intervals) revealed distinctly different profiles for the different age groups (50 Hz: p = 3.3*10−5; 100 Hz: p = 0.071, one-way ANOVA). PPD at 50 Hz (Fig. 6C) was significantly larger in P1-2 than in P3-4 cells (p = 0.014) and in P5-8 than in P9-12 cells (p = 0.041; [Paired-pulse ratios at 50 Hz: P1-P2, 0.36±0.06; P3-P4, 0.58±0.05; P5-P8, 0.65±0.05; P9-P12, 0.84±0.07]). At 100 Hz, PPD was also significantly larger in P1-2 and in P3-4 cells than in P9-12 cells (p = 0.0018; p = 0.012; [Paired-pulse ratios at 100 Hz: P1-P2, 0.19±0.03; P3-P4, 0.28±0.07; P5-P8, 0.32±0.12; P9-P12, 0.66±0.10]). These data suggest that changes in probability of neurotransmitter release, rate of vesicle recruitment, number of postsynaptic receptors, or some combination of these, follow a developmental trend that coincides with functional refinement at VCN-LSO synapses.


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)

Paired-pulse depression decreases between birth and hearing onset.A: Representative responses to 50 Hz pulse-trains in P2, P5, and P9 cells; responses to the first five pulses only are shown. Greater paired-pulse depression between pulse 1 and 2 is evident in the youngest cell than in the older cells. B: Average responses to 10-pulse trains at four frequencies. At stimulation frequencies of 20 Hz or less, few differences are seen between ages. At 50 and 100 Hz, clear differences are obvious between age groups, and only the oldest (P9-12) cells are able to follow 100 Hz trains. C: Group data from B, showing paired-pulse ratios as pulse 2/pulse 1. At 10 and 20 Hz, age differences are not significant at the p<0.05 level (p = 0.48 and p = 0.063, one-way ANOVA). At 50 Hz, significant age differences are seen in paired-pulse depression (one-way ANOVA:  = 3.3*10−5), with greater depression in P1-2 slices than in P3-4 slices (posthoc Mann-Whitney p = 0.014) and in P5-8 slices than in P9-12 slices (p = 0.041). At 100 Hz, significant age differences are also seen (one-way ANOVA p = 0.071), with paired-pulse depression greater in P1-2 (p = 0.0018) and P3-4 slices than in P9-12 slices (p = 0.012).
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Related In: Results  -  Collection

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pone-0020756-g006: Paired-pulse depression decreases between birth and hearing onset.A: Representative responses to 50 Hz pulse-trains in P2, P5, and P9 cells; responses to the first five pulses only are shown. Greater paired-pulse depression between pulse 1 and 2 is evident in the youngest cell than in the older cells. B: Average responses to 10-pulse trains at four frequencies. At stimulation frequencies of 20 Hz or less, few differences are seen between ages. At 50 and 100 Hz, clear differences are obvious between age groups, and only the oldest (P9-12) cells are able to follow 100 Hz trains. C: Group data from B, showing paired-pulse ratios as pulse 2/pulse 1. At 10 and 20 Hz, age differences are not significant at the p<0.05 level (p = 0.48 and p = 0.063, one-way ANOVA). At 50 Hz, significant age differences are seen in paired-pulse depression (one-way ANOVA:  = 3.3*10−5), with greater depression in P1-2 slices than in P3-4 slices (posthoc Mann-Whitney p = 0.014) and in P5-8 slices than in P9-12 slices (p = 0.041). At 100 Hz, significant age differences are also seen (one-way ANOVA p = 0.071), with paired-pulse depression greater in P1-2 (p = 0.0018) and P3-4 slices than in P9-12 slices (p = 0.012).
Mentions: Circuits in the auditory brainstem are capable of supporting among the fastest firing rates in the nervous system. Additionally, varying patterns of activity in the mouse VCN-LSO pathway have been shown to differentially activate different glutamate receptor subtypes and different calcium sources [28]. To determine the capability of VCN-LSO synapses to support repetitive activity in the developing circuit, we added cyclothiazide to the perfusate to prevent AMPAR desensitization and measured responses to 50 Hz pulse-train stimuli delivered to the ventral acoustic stria. As judged by paired-pulse depression (PPD), neurons in the youngest slices were unable to follow at 50 Hz, a relatively slow frequency for the auditory brainstem (Fig. 6A). In order to ask how frequency-following matures between P1 and P12 we delivered pulse trains of 10 stimuli at 10, 20, 50, and 100 Hz to VCN-LSO fibers. Stimulation at lower frequencies (10 and 20 Hz, or 100 and 50 ms inter-stimulus intervals) yielded similar response profiles at all ages (Fig. 6B), whereas stimulation at higher frequencies (50 and 100 Hz, or 20 and 10 ms inter-stimulus intervals) revealed distinctly different profiles for the different age groups (50 Hz: p = 3.3*10−5; 100 Hz: p = 0.071, one-way ANOVA). PPD at 50 Hz (Fig. 6C) was significantly larger in P1-2 than in P3-4 cells (p = 0.014) and in P5-8 than in P9-12 cells (p = 0.041; [Paired-pulse ratios at 50 Hz: P1-P2, 0.36±0.06; P3-P4, 0.58±0.05; P5-P8, 0.65±0.05; P9-P12, 0.84±0.07]). At 100 Hz, PPD was also significantly larger in P1-2 and in P3-4 cells than in P9-12 cells (p = 0.0018; p = 0.012; [Paired-pulse ratios at 100 Hz: P1-P2, 0.19±0.03; P3-P4, 0.28±0.07; P5-P8, 0.32±0.12; P9-P12, 0.66±0.10]). These data suggest that changes in probability of neurotransmitter release, rate of vesicle recruitment, number of postsynaptic receptors, or some combination of these, follow a developmental trend that coincides with functional refinement at VCN-LSO synapses.

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