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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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Examples of IAP for simulated, AVCN, and MNTB recordings of spontaneous activity.The left column shows voltage traces (black) and trigger levels for complex (red) and candidate waveforms (orange) for each unit. The corresponding average complex waveform (black) and its pointwise standard deviation (gray) is depicted in the middle column. The trigger potential (TP) (MNTB: presynaptic spike, AVCN: postsynaptic potential, probably the EPSC) is also indicated. The right column shows the histograms (orange) generated by triggering at the height of the TP (after aligned subtraction of the average complex waveform). Further the interspike interval histograms of the complex waveforms are shown, mainly for visual comparison. For the simulated data (A2, B2) the histograms reflect the failure containing condition by a decrease in CritWin (A2), and conversely the lack of decrease in the two unit condition (B2). Guided by the results from the known datasets, the AVCN data (C2, D2) can be interpreted: A substantial number of cells exhibited histograms similar to the cell in C2, suggesting failures of transmission, while the remaining cells showed histograms similar to the cell in D2. If a decrease occurred, its timing was predicted by the ISI histogram (blue). In the MNTB (E2, F2, G2) the most frequent finding was the absence of iP at the TPs height, leading to an empty histogram as in E2. Most of the units with iPs of sufficient height, exhibited no decrease of the histogram in CritWin, as in F2. In a small fraction of recordings a decrease was observed, yet, this could be accompanied by unusually high variability in timing from the presynaptic to the postsynaptic side as in G2 (see individual trace in middle column). IAP classified the recordings in A,B, and G as Dep and the remaining as no Dep.
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pone-0007014-g005: Examples of IAP for simulated, AVCN, and MNTB recordings of spontaneous activity.The left column shows voltage traces (black) and trigger levels for complex (red) and candidate waveforms (orange) for each unit. The corresponding average complex waveform (black) and its pointwise standard deviation (gray) is depicted in the middle column. The trigger potential (TP) (MNTB: presynaptic spike, AVCN: postsynaptic potential, probably the EPSC) is also indicated. The right column shows the histograms (orange) generated by triggering at the height of the TP (after aligned subtraction of the average complex waveform). Further the interspike interval histograms of the complex waveforms are shown, mainly for visual comparison. For the simulated data (A2, B2) the histograms reflect the failure containing condition by a decrease in CritWin (A2), and conversely the lack of decrease in the two unit condition (B2). Guided by the results from the known datasets, the AVCN data (C2, D2) can be interpreted: A substantial number of cells exhibited histograms similar to the cell in C2, suggesting failures of transmission, while the remaining cells showed histograms similar to the cell in D2. If a decrease occurred, its timing was predicted by the ISI histogram (blue). In the MNTB (E2, F2, G2) the most frequent finding was the absence of iP at the TPs height, leading to an empty histogram as in E2. Most of the units with iPs of sufficient height, exhibited no decrease of the histogram in CritWin, as in F2. In a small fraction of recordings a decrease was observed, yet, this could be accompanied by unusually high variability in timing from the presynaptic to the postsynaptic side as in G2 (see individual trace in middle column). IAP classified the recordings in A,B, and G as Dep and the remaining as no Dep.

Mentions: The following representative results for a Dep and a No Dep simulation serve to provide intuition for the subsequent interpretation of IAP results of experimental data where the exact dependence between CWs and iPs is unknown (Figure 5A, B). We created simulated data sets closely mimicking voltage traces of AVCN/MNTB units. In these data sets, all parameters can be controlled, especially the dependence between CWs and iPs. In both examples, the CW and the iP firing rates were constant at 50 Hz and periods of 100 s were simulated.


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)

Examples of IAP for simulated, AVCN, and MNTB recordings of spontaneous activity.The left column shows voltage traces (black) and trigger levels for complex (red) and candidate waveforms (orange) for each unit. The corresponding average complex waveform (black) and its pointwise standard deviation (gray) is depicted in the middle column. The trigger potential (TP) (MNTB: presynaptic spike, AVCN: postsynaptic potential, probably the EPSC) is also indicated. The right column shows the histograms (orange) generated by triggering at the height of the TP (after aligned subtraction of the average complex waveform). Further the interspike interval histograms of the complex waveforms are shown, mainly for visual comparison. For the simulated data (A2, B2) the histograms reflect the failure containing condition by a decrease in CritWin (A2), and conversely the lack of decrease in the two unit condition (B2). Guided by the results from the known datasets, the AVCN data (C2, D2) can be interpreted: A substantial number of cells exhibited histograms similar to the cell in C2, suggesting failures of transmission, while the remaining cells showed histograms similar to the cell in D2. If a decrease occurred, its timing was predicted by the ISI histogram (blue). In the MNTB (E2, F2, G2) the most frequent finding was the absence of iP at the TPs height, leading to an empty histogram as in E2. Most of the units with iPs of sufficient height, exhibited no decrease of the histogram in CritWin, as in F2. In a small fraction of recordings a decrease was observed, yet, this could be accompanied by unusually high variability in timing from the presynaptic to the postsynaptic side as in G2 (see individual trace in middle column). IAP classified the recordings in A,B, and G as Dep and the remaining as no Dep.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2749334&req=5

pone-0007014-g005: Examples of IAP for simulated, AVCN, and MNTB recordings of spontaneous activity.The left column shows voltage traces (black) and trigger levels for complex (red) and candidate waveforms (orange) for each unit. The corresponding average complex waveform (black) and its pointwise standard deviation (gray) is depicted in the middle column. The trigger potential (TP) (MNTB: presynaptic spike, AVCN: postsynaptic potential, probably the EPSC) is also indicated. The right column shows the histograms (orange) generated by triggering at the height of the TP (after aligned subtraction of the average complex waveform). Further the interspike interval histograms of the complex waveforms are shown, mainly for visual comparison. For the simulated data (A2, B2) the histograms reflect the failure containing condition by a decrease in CritWin (A2), and conversely the lack of decrease in the two unit condition (B2). Guided by the results from the known datasets, the AVCN data (C2, D2) can be interpreted: A substantial number of cells exhibited histograms similar to the cell in C2, suggesting failures of transmission, while the remaining cells showed histograms similar to the cell in D2. If a decrease occurred, its timing was predicted by the ISI histogram (blue). In the MNTB (E2, F2, G2) the most frequent finding was the absence of iP at the TPs height, leading to an empty histogram as in E2. Most of the units with iPs of sufficient height, exhibited no decrease of the histogram in CritWin, as in F2. In a small fraction of recordings a decrease was observed, yet, this could be accompanied by unusually high variability in timing from the presynaptic to the postsynaptic side as in G2 (see individual trace in middle column). IAP classified the recordings in A,B, and G as Dep and the remaining as no Dep.
Mentions: The following representative results for a Dep and a No Dep simulation serve to provide intuition for the subsequent interpretation of IAP results of experimental data where the exact dependence between CWs and iPs is unknown (Figure 5A, B). We created simulated data sets closely mimicking voltage traces of AVCN/MNTB units. In these data sets, all parameters can be controlled, especially the dependence between CWs and iPs. In both examples, the CW and the iP firing rates were constant at 50 Hz and periods of 100 s were simulated.

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