Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration.
Neurons spike when their membrane potential exceeds a threshold value. In central neurons, the spike threshold is not constant but depends on the stimulation. Thus, input-output properties of neurons depend both on the effect of presynaptic spikes on the membrane potential and on the dynamics of the...
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Public Library of Science (PLoS)
2011-05-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1001129&type=printable |
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| author | Jonathan Platkiewicz Romain Brette |
| author_facet | Jonathan Platkiewicz Romain Brette |
| author_sort | Jonathan Platkiewicz |
| collection | DOAJ |
| description | Neurons spike when their membrane potential exceeds a threshold value. In central neurons, the spike threshold is not constant but depends on the stimulation. Thus, input-output properties of neurons depend both on the effect of presynaptic spikes on the membrane potential and on the dynamics of the spike threshold. Among the possible mechanisms that may modulate the threshold, one strong candidate is Na channel inactivation, because it specifically impacts spike initiation without affecting the membrane potential. We collected voltage-clamp data from the literature and we found, based on a theoretical criterion, that the properties of Na inactivation could indeed cause substantial threshold variability by itself. By analyzing simple neuron models with fast Na inactivation (one channel subtype), we found that the spike threshold is correlated with the mean membrane potential and negatively correlated with the preceding depolarization slope, consistent with experiments. We then analyzed the impact of threshold dynamics on synaptic integration. The difference between the postsynaptic potential (PSP) and the dynamic threshold in response to a presynaptic spike defines an effective PSP. When the neuron is sufficiently depolarized, this effective PSP is briefer than the PSP. This mechanism regulates the temporal window of synaptic integration in an adaptive way. Finally, we discuss the role of other potential mechanisms. Distal spike initiation, channel noise and Na activation dynamics cannot account for the observed negative slope-threshold relationship, while adaptive conductances (e.g. K+) and Na inactivation can. We conclude that Na inactivation is a metabolically efficient mechanism to control the temporal resolution of synaptic integration. |
| format | Article |
| id | doaj-art-b4b1227d94ab42dfb30f7bc7ff87be15 |
| institution | DOAJ |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2011-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-b4b1227d94ab42dfb30f7bc7ff87be152025-08-20T03:10:02ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582011-05-0175e100112910.1371/journal.pcbi.1001129Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration.Jonathan PlatkiewiczRomain BretteNeurons spike when their membrane potential exceeds a threshold value. In central neurons, the spike threshold is not constant but depends on the stimulation. Thus, input-output properties of neurons depend both on the effect of presynaptic spikes on the membrane potential and on the dynamics of the spike threshold. Among the possible mechanisms that may modulate the threshold, one strong candidate is Na channel inactivation, because it specifically impacts spike initiation without affecting the membrane potential. We collected voltage-clamp data from the literature and we found, based on a theoretical criterion, that the properties of Na inactivation could indeed cause substantial threshold variability by itself. By analyzing simple neuron models with fast Na inactivation (one channel subtype), we found that the spike threshold is correlated with the mean membrane potential and negatively correlated with the preceding depolarization slope, consistent with experiments. We then analyzed the impact of threshold dynamics on synaptic integration. The difference between the postsynaptic potential (PSP) and the dynamic threshold in response to a presynaptic spike defines an effective PSP. When the neuron is sufficiently depolarized, this effective PSP is briefer than the PSP. This mechanism regulates the temporal window of synaptic integration in an adaptive way. Finally, we discuss the role of other potential mechanisms. Distal spike initiation, channel noise and Na activation dynamics cannot account for the observed negative slope-threshold relationship, while adaptive conductances (e.g. K+) and Na inactivation can. We conclude that Na inactivation is a metabolically efficient mechanism to control the temporal resolution of synaptic integration.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1001129&type=printable |
| spellingShingle | Jonathan Platkiewicz Romain Brette Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration. PLoS Computational Biology |
| title | Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration. |
| title_full | Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration. |
| title_fullStr | Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration. |
| title_full_unstemmed | Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration. |
| title_short | Impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration. |
| title_sort | impact of fast sodium channel inactivation on spike threshold dynamics and synaptic integration |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1001129&type=printable |
| work_keys_str_mv | AT jonathanplatkiewicz impactoffastsodiumchannelinactivationonspikethresholddynamicsandsynapticintegration AT romainbrette impactoffastsodiumchannelinactivationonspikethresholddynamicsandsynapticintegration |