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

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README.md

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

Timescale of spike amplitude decay

Extended activation of rodent cortical neurons led to a slow spike amplitude reduction.

Rodent cortical neurons were activated for 40 seconds using short (2 ms) depolarizing current pulses (3 nA) generated at 40 Hz.

These neurons exhibited a slow and progressive reduction in spike amplitude that was best fit by a double exponential decay. The fast and the slow components of the spike amplitude decay were calculated by fitting the time dependent spike-voltage-peak to a double exponential function,

represents the spike peak at the steady state (when the spike peak is not decaying anymore). The sum yields the spike peak at stimulus onset. is the fast time constant of the spike amplitude decay, and is the slow time constant of the spike amplitude decay.

The parameters that yielded the best fit for the spike amplitude decay were calculated for all the cells measured (notebook p_graphs_spkAmplDecay_time_scales.ipynb).

Extracellular potassium dependent spiking irregularity

Spiking irregularity increased with increases of the extracellular potassium concentration. Current-induced activity in mouse cortical pyramidal neurons exposed to different fixed concentrations of extracellular potassium was recorded. Action potentials were induced by constant-current stimulation in baseline conditions (3 mM extracellular potassium), and after increasing the concentration of extracellular potassium to 10 or 12 mM. Neurons were stimulated with somatic current injection sufficient to maintain the membrane potential close to spiking threshold.

Spiking irregularity was quantified in all the neurons recorded with the coefficient of variation (CV);

where is the standard deviation of the interspike interval (ISI), and is the mean.

An example is shown in (notebook p_graphs_Ko_dependent_Irregularity.ipynb).

Simulations

The code to reproduce the simulations reported in the manuscript can be found in https://itbgit.biologie.hu-berlin.de/contreras/activity-mediated_accumulation_potassium_induces_switch_firing .

datacite.yml
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