Limits...
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.

Show MeSH

Related in: MedlinePlus

AMPARs contain GluA2 subunits.A: Example AMPAR responses at various holding potentials for cells with low (left) and high (right) rectification indices. Rectification indices indicate that AMPARs contain GluA2 subunits during the period of VCN-LSO input functional refinement (n = 21). B: Rectification indices of pharmacologically isolated AMPAR responses (average RI = 0.83±0.03, n = 21, P1-12). Symbols corresponding to cells shown in A are shaded. C: Representative recording from a cell (P1) in response to high-frequency stimulation in an attempt to activate mGluRs. With CNQX and APV in the perfusate, stimulation at 100 Hz failed to elicit mGluR-mediated currents in any cell thus examined (n = 21).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3111428&req=5

pone-0020756-g005: AMPARs contain GluA2 subunits.A: Example AMPAR responses at various holding potentials for cells with low (left) and high (right) rectification indices. Rectification indices indicate that AMPARs contain GluA2 subunits during the period of VCN-LSO input functional refinement (n = 21). B: Rectification indices of pharmacologically isolated AMPAR responses (average RI = 0.83±0.03, n = 21, P1-12). Symbols corresponding to cells shown in A are shaded. C: Representative recording from a cell (P1) in response to high-frequency stimulation in an attempt to activate mGluRs. With CNQX and APV in the perfusate, stimulation at 100 Hz failed to elicit mGluR-mediated currents in any cell thus examined (n = 21).

Mentions: We asked whether other glutamate receptors known to mediate synaptic plasticity, such as either the GluA2-lacking, calcium-permeable AMPARs (CP-AMPARs) or the metabotropic glutamate receptors (mGluRs), might contribute to the EPSCs measured after stimulation of VCN-LSO fibers. After applying APV to isolate the AMPAR-mediated response, we obtained current-voltage relationships and used subunit-specific pharmacology to test for the presence of CP-AMPARs at VCN-LSO synapses (Fig. 5A). AMPARs did not exhibit substantial inward rectification at any age examined (Fig. 5B; mean RI = 0.83±0.03, n = 21). Despite an apparent trend toward lower rectification indices (RIs) immediately before hearing onset, no significant age-dependent effects were seen (Kruskal-Wallis for age effects: p = 0.13). Additionally, the CP-AMPAR specific antagonist IEM 1460 had no effect on AMPAR-mediated currents at any age (% reduction = 7.0±6.6%, n = 10; data not shown). These data agree with earlier Ca++-imaging results in neonatal mouse VCN-LSO showing that AMPAR-elicited Ca++ transients are not due to influx through CP-AMPARs [28].


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)

AMPARs contain GluA2 subunits.A: Example AMPAR responses at various holding potentials for cells with low (left) and high (right) rectification indices. Rectification indices indicate that AMPARs contain GluA2 subunits during the period of VCN-LSO input functional refinement (n = 21). B: Rectification indices of pharmacologically isolated AMPAR responses (average RI = 0.83±0.03, n = 21, P1-12). Symbols corresponding to cells shown in A are shaded. C: Representative recording from a cell (P1) in response to high-frequency stimulation in an attempt to activate mGluRs. With CNQX and APV in the perfusate, stimulation at 100 Hz failed to elicit mGluR-mediated currents in any cell thus examined (n = 21).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111428&req=5

pone-0020756-g005: AMPARs contain GluA2 subunits.A: Example AMPAR responses at various holding potentials for cells with low (left) and high (right) rectification indices. Rectification indices indicate that AMPARs contain GluA2 subunits during the period of VCN-LSO input functional refinement (n = 21). B: Rectification indices of pharmacologically isolated AMPAR responses (average RI = 0.83±0.03, n = 21, P1-12). Symbols corresponding to cells shown in A are shaded. C: Representative recording from a cell (P1) in response to high-frequency stimulation in an attempt to activate mGluRs. With CNQX and APV in the perfusate, stimulation at 100 Hz failed to elicit mGluR-mediated currents in any cell thus examined (n = 21).
Mentions: We asked whether other glutamate receptors known to mediate synaptic plasticity, such as either the GluA2-lacking, calcium-permeable AMPARs (CP-AMPARs) or the metabotropic glutamate receptors (mGluRs), might contribute to the EPSCs measured after stimulation of VCN-LSO fibers. After applying APV to isolate the AMPAR-mediated response, we obtained current-voltage relationships and used subunit-specific pharmacology to test for the presence of CP-AMPARs at VCN-LSO synapses (Fig. 5A). AMPARs did not exhibit substantial inward rectification at any age examined (Fig. 5B; mean RI = 0.83±0.03, n = 21). Despite an apparent trend toward lower rectification indices (RIs) immediately before hearing onset, no significant age-dependent effects were seen (Kruskal-Wallis for age effects: p = 0.13). Additionally, the CP-AMPAR specific antagonist IEM 1460 had no effect on AMPAR-mediated currents at any age (% reduction = 7.0±6.6%, n = 10; data not shown). These data agree with earlier Ca++-imaging results in neonatal mouse VCN-LSO showing that AMPAR-elicited Ca++ transients are not due to influx through CP-AMPARs [28].

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