doi/Activity-mediated_accumulation_potassium_induces_switch_firing_pattern: Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type

Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type

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				Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type

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Title	Recordings shown in "Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type "
Authors	Contreras Ceballos,Susana Andrea;Institute for Theoretical Biology, Humboldt-University of Berlin; Bernstein Center for Computational Neuroscience Berlin;ORCID:0000-0002-1819-0899 Schleimer,Jan-Hendrik;Institute for Theoretical Biology, Humboldt-University of Berlin; Bernstein Center for Computational Neuroscience Berlin;ORCID:0000-0002-2156-330X Gulledge,Allan T;Molecular and Systems Biology, Geisel School of Medicine at Dartmouth College;ORCID:0000-0002-5721-374X Schreiber,Susanne;Institute for Theoretical Biology, Humboldt-University of Berlin; Bernstein Center for Computational Neuroscience Berlin;ORCID:0000-0003-3913-5650
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 here investigate 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 that previously had been attributed soley to sodium channel inactivation; (ii) extracellular potassium accumulation switches action potential generation from tonic firing to intermittently interrupted output. Individual neurons thus may respond very differently to the same input stimuli, depending on their recent patterns of activity or the current brain-state.
License	Creative Commons CC0 1.0 Public Domain Dedication (https://creativecommons.org/publicdomain/zero/1.0/)
References	Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type [doi:10.1101/2020.11.30.403782] (IsSupplementTo)
Funding	BMBF, BMBF.01GQ1403 ERC, ERC.864243 R01, MH099054 GRK, 1589/2
Keywords	conductance-based modelling onset bifurcation adaptation extracellular space extracellular potassium concentration spiking irregularity spike amplitude reduction sodium accumulation slow-fast analysis bistability
Resource Type	Dataset