Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type.
During normal neuronal activity, ionic concentration gradients across a neuron's membrane are often assumed to be stable. Prolonged spiking activity, however, can reduce transmembrane gradients and affect voltage dynamics. Based on mathematical modeling, we investigated the impact of neuronal a...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-05-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008510&type=printable |
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| author | Susana Andrea Contreras Jan-Hendrik Schleimer Allan T Gulledge Susanne Schreiber |
| author_facet | Susana Andrea Contreras Jan-Hendrik Schleimer Allan T Gulledge Susanne Schreiber |
| author_sort | Susana Andrea Contreras |
| collection | DOAJ |
| description | During normal neuronal activity, ionic concentration gradients across a neuron's membrane are often assumed to be stable. Prolonged spiking activity, however, can reduce transmembrane gradients and affect voltage dynamics. Based on mathematical modeling, we investigated the impact of neuronal activity on ionic concentrations and, consequently, the dynamics of action potential generation. We find that intense spiking activity on the order of a second suffices to induce changes in ionic reversal potentials and to consistently induce a switch from a regular to an intermittent firing mode. This transition is caused by a qualitative alteration in the system's voltage dynamics, mathematically corresponding to a co-dimension-two bifurcation from a saddle-node on invariant cycle (SNIC) to a homoclinic orbit bifurcation (HOM). Our electrophysiological recordings in mouse cortical pyramidal neurons confirm the changes in action potential dynamics predicted by the models: (i) activity-dependent increases in intracellular sodium concentration directly reduce action potential amplitudes, an effect typically attributed solely to sodium channel inactivation; (ii) extracellular potassium accumulation switches action potential generation from tonic firing to intermittently interrupted output. Thus, individual neurons may respond very differently to the same input stimuli, depending on their recent patterns of activity and/or the current brain-state. |
| format | Article |
| id | doaj-art-c6335de2418c40409042afdd18abfc90 |
| institution | OA Journals |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2021-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-c6335de2418c40409042afdd18abfc902025-08-20T02:01:04ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-05-01175e100851010.1371/journal.pcbi.1008510Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type.Susana Andrea ContrerasJan-Hendrik SchleimerAllan T GulledgeSusanne SchreiberDuring normal neuronal activity, ionic concentration gradients across a neuron's membrane are often assumed to be stable. Prolonged spiking activity, however, can reduce transmembrane gradients and affect voltage dynamics. Based on mathematical modeling, we investigated the impact of neuronal activity on ionic concentrations and, consequently, the dynamics of action potential generation. We find that intense spiking activity on the order of a second suffices to induce changes in ionic reversal potentials and to consistently induce a switch from a regular to an intermittent firing mode. This transition is caused by a qualitative alteration in the system's voltage dynamics, mathematically corresponding to a co-dimension-two bifurcation from a saddle-node on invariant cycle (SNIC) to a homoclinic orbit bifurcation (HOM). Our electrophysiological recordings in mouse cortical pyramidal neurons confirm the changes in action potential dynamics predicted by the models: (i) activity-dependent increases in intracellular sodium concentration directly reduce action potential amplitudes, an effect typically attributed solely to sodium channel inactivation; (ii) extracellular potassium accumulation switches action potential generation from tonic firing to intermittently interrupted output. Thus, individual neurons may respond very differently to the same input stimuli, depending on their recent patterns of activity and/or the current brain-state.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008510&type=printable |
| spellingShingle | Susana Andrea Contreras Jan-Hendrik Schleimer Allan T Gulledge Susanne Schreiber Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type. PLoS Computational Biology |
| title | Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type. |
| title_full | Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type. |
| title_fullStr | Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type. |
| title_full_unstemmed | Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type. |
| title_short | Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type. |
| title_sort | activity mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008510&type=printable |
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