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Reliability of synaptic transmission at the synapses of Held in vivo under acoustic stimulation.

Englitz B, Tolnai S, Typlt M, Jost J, Rübsamen R - PLoS ONE (2009)

Bottom Line: Its performance is quantified using simulated voltage recordings and found to exhibit a high level of accuracy.By contrast, at the endbulbs of Held in the AVCN failures were found under spontaneous, excited, and suppressed conditions.In accordance with previous studies, failures occurred most abundantly in the suppressed condition, suggesting a role for inhibition.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Mathematics in the Sciences, Leipzig, Germany.

ABSTRACT

Background: The giant synapses of Held play an important role in high-fidelity auditory processing and provide a model system for synaptic transmission at central synapses. Whether transmission of action potentials can fail at these synapses has been investigated in recent studies. At the endbulbs of Held in the anteroventral cochlear nucleus (AVCN) a consistent picture emerged, whereas at the calyx of Held in the medial nucleus of the trapezoid body (MNTB) results on the reliability of transmission remain inconsistent. In vivo this discrepancy could be due to the difficulty in identifying failures of transmission.

Methods/findings: We introduce a novel method for detecting unreliable transmission in vivo. Based on the temporal relationship between a cells' waveform and other potentials in the recordings, a statistical test is developed that provides a balanced decision between the presence and the absence of failures. Its performance is quantified using simulated voltage recordings and found to exhibit a high level of accuracy. The method was applied to extracellular recordings from the synapses of Held in vivo. At the calyces of Held failures of transmission were found only rarely. By contrast, at the endbulbs of Held in the AVCN failures were found under spontaneous, excited, and suppressed conditions. In accordance with previous studies, failures occurred most abundantly in the suppressed condition, suggesting a role for inhibition.

Conclusions/significance: Under the investigated activity conditions/anesthesia, transmission seems to remain largely unimpeded in the MNTB, whereas in the AVCN the occurrence of failures is related to inhibition and could be the basis/result of computational mechanisms for temporal processing. More generally, our approach provides a formal tool for studying the reliability of transmission with high statistical accuracy under typical in vivo recording conditions.

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Related in: MedlinePlus

IAP decision level .(A)  is determined by the intersection of the β-error distributions for the two cases Dep (blue, corresponding to failures) and No Dep (orange, corresponding to two units) which were generated from simulated voltage recordings. (B) Average  assigned by IAP to simulations with matched parameters (colors as above). On average, IAP separates Dep and No Dep for all values of the total number of iPs in the RefWin and CritWin () and the signal-to-noise ratio of the TP (SNR). (C) One-sided 5% β-error surfaces for Dep and No Dep. The curve of intersection between these surfaces marks the parameter combinations where the common β-error drops below 5%, the criterion for including recordings. If  of a given recording lies below the surface of equal β-errors (yellow), it is classified as Dep, otherwise as No Dep.
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pone-0007014-g003: IAP decision level .(A) is determined by the intersection of the β-error distributions for the two cases Dep (blue, corresponding to failures) and No Dep (orange, corresponding to two units) which were generated from simulated voltage recordings. (B) Average assigned by IAP to simulations with matched parameters (colors as above). On average, IAP separates Dep and No Dep for all values of the total number of iPs in the RefWin and CritWin () and the signal-to-noise ratio of the TP (SNR). (C) One-sided 5% β-error surfaces for Dep and No Dep. The curve of intersection between these surfaces marks the parameter combinations where the common β-error drops below 5%, the criterion for including recordings. If of a given recording lies below the surface of equal β-errors (yellow), it is classified as Dep, otherwise as No Dep.

Mentions: While behaves similar to a probability, indicating whether to maintain the 0-hypothesis of independent iPs/no rate reduction, it is not a proper probability. Even if it were a probability, we would need to choose a significance level at which to reject the 0-hypothesis. Rather than rejecting one alternative, we determined a decision point which minimizes the probability of an incorrect decision for the two hypotheses, i.e. with such that , where denotes the false rejection (Type II) error given that the hypothesis is true (1) or false (0) for the decision point S (see Figure 3A). The significance level of the test is then automatically upper bounded by . To determine it was necessary to estimate the distributions of for dependent and independent iPs based on simulated voltage recordings (details are provided below).


Reliability of synaptic transmission at the synapses of Held in vivo under acoustic stimulation.

Englitz B, Tolnai S, Typlt M, Jost J, Rübsamen R - PLoS ONE (2009)

IAP decision level .(A)  is determined by the intersection of the β-error distributions for the two cases Dep (blue, corresponding to failures) and No Dep (orange, corresponding to two units) which were generated from simulated voltage recordings. (B) Average  assigned by IAP to simulations with matched parameters (colors as above). On average, IAP separates Dep and No Dep for all values of the total number of iPs in the RefWin and CritWin () and the signal-to-noise ratio of the TP (SNR). (C) One-sided 5% β-error surfaces for Dep and No Dep. The curve of intersection between these surfaces marks the parameter combinations where the common β-error drops below 5%, the criterion for including recordings. If  of a given recording lies below the surface of equal β-errors (yellow), it is classified as Dep, otherwise as No Dep.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2749334&req=5

pone-0007014-g003: IAP decision level .(A) is determined by the intersection of the β-error distributions for the two cases Dep (blue, corresponding to failures) and No Dep (orange, corresponding to two units) which were generated from simulated voltage recordings. (B) Average assigned by IAP to simulations with matched parameters (colors as above). On average, IAP separates Dep and No Dep for all values of the total number of iPs in the RefWin and CritWin () and the signal-to-noise ratio of the TP (SNR). (C) One-sided 5% β-error surfaces for Dep and No Dep. The curve of intersection between these surfaces marks the parameter combinations where the common β-error drops below 5%, the criterion for including recordings. If of a given recording lies below the surface of equal β-errors (yellow), it is classified as Dep, otherwise as No Dep.
Mentions: While behaves similar to a probability, indicating whether to maintain the 0-hypothesis of independent iPs/no rate reduction, it is not a proper probability. Even if it were a probability, we would need to choose a significance level at which to reject the 0-hypothesis. Rather than rejecting one alternative, we determined a decision point which minimizes the probability of an incorrect decision for the two hypotheses, i.e. with such that , where denotes the false rejection (Type II) error given that the hypothesis is true (1) or false (0) for the decision point S (see Figure 3A). The significance level of the test is then automatically upper bounded by . To determine it was necessary to estimate the distributions of for dependent and independent iPs based on simulated voltage recordings (details are provided below).

Bottom Line: Its performance is quantified using simulated voltage recordings and found to exhibit a high level of accuracy.By contrast, at the endbulbs of Held in the AVCN failures were found under spontaneous, excited, and suppressed conditions.In accordance with previous studies, failures occurred most abundantly in the suppressed condition, suggesting a role for inhibition.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Mathematics in the Sciences, Leipzig, Germany.

ABSTRACT

Background: The giant synapses of Held play an important role in high-fidelity auditory processing and provide a model system for synaptic transmission at central synapses. Whether transmission of action potentials can fail at these synapses has been investigated in recent studies. At the endbulbs of Held in the anteroventral cochlear nucleus (AVCN) a consistent picture emerged, whereas at the calyx of Held in the medial nucleus of the trapezoid body (MNTB) results on the reliability of transmission remain inconsistent. In vivo this discrepancy could be due to the difficulty in identifying failures of transmission.

Methods/findings: We introduce a novel method for detecting unreliable transmission in vivo. Based on the temporal relationship between a cells' waveform and other potentials in the recordings, a statistical test is developed that provides a balanced decision between the presence and the absence of failures. Its performance is quantified using simulated voltage recordings and found to exhibit a high level of accuracy. The method was applied to extracellular recordings from the synapses of Held in vivo. At the calyces of Held failures of transmission were found only rarely. By contrast, at the endbulbs of Held in the AVCN failures were found under spontaneous, excited, and suppressed conditions. In accordance with previous studies, failures occurred most abundantly in the suppressed condition, suggesting a role for inhibition.

Conclusions/significance: Under the investigated activity conditions/anesthesia, transmission seems to remain largely unimpeded in the MNTB, whereas in the AVCN the occurrence of failures is related to inhibition and could be the basis/result of computational mechanisms for temporal processing. More generally, our approach provides a formal tool for studying the reliability of transmission with high statistical accuracy under typical in vivo recording conditions.

Show MeSH
Related in: MedlinePlus