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

2021 ◽  
Vol 17 (5) ◽  
pp. e1008510
Author(s):  
Susana Andrea Contreras ◽  
Jan-Hendrik Schleimer ◽  
Allan T. Gulledge ◽  
Susanne Schreiber
Keyword(s):  
Action Potential ◽  
Neuronal Activity ◽  
Brain State ◽  
Extracellular Potassium ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Potassium Accumulation ◽  
Voltage Dynamics ◽  
The Impact ◽  
Spiking Activity

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.

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

2020 ◽  
Author(s):  
Susana Andrea Contreras ◽  
Jan-Hendrik Schleimer ◽  
Allan T. Gulledge ◽  
Susanne Schreiber
Keyword(s):  
Action Potential ◽  
Neuronal Activity ◽  
Brain State ◽  
Extracellular Potassium ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Ionic Concentrations ◽  
Channel Inactivation ◽  
Firing Mode ◽  
Voltage Dynamics

AbstractDuring 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.Author summaryIonic concentrations in the brain are not constant. We show that during intense neuronal activity, they can change on the order of seconds and even switch neuronal spiking patterns under identical stimulation from a regular firing mode to an intermittently interrupted one. Triggered by an accumulation of extracellular potassium, such a transition is caused by a specific, qualitative change in of the neuronal voltage dynamics – a so-called bifurcation – which affects crucial features of action-potential generation and bears consequences for how information is encoded and how neurons behave together in the network. Also changes in intracellular sodium can induce measurable effects, like a shrinkage of spike amplitude that occurs independently of the fast amplitude-effects attributed to sodium channel inactivation. Taken together, our results demonstrate that a neuron can respond very differently to the same stimulus, depending on its previous activity or the current brain state. The finding is particularly relevant when other regulatory mechanisms of ionic homeostasis are challenged, for example, during pathological states of glial impairment or oxygen deprivation. Categorization of cortical neurons as intrinsically bursting or regular spiking may be biased by the ionic concentrations at the time of the observation, highlighting the non-static nature of neuronal dynamics.

scholarly journals Patterned activation of action potential patterns during offline states in the neocortex: replay and non-replay

2020 ◽  
Vol 375 (1799) ◽  
pp. 20190233 ◽  
Author(s):  
Tang-Yu Liu ◽  
Brendon O. Watson
Keyword(s):  
Action Potential ◽  
Memory Consolidation ◽  
Brain State ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Cortical Networks ◽  
Memory Reactivation ◽  
State Changes ◽  
Random Patterns ◽  
Repeating Patterns

Action potential generation (spiking) in the neocortex is organized into repeating non-random patterns during both awake experiential states and non-engaged states ranging from inattention to sleep to anaesthesia—and even occur in slice preparations. Repeating patterns in a given population of neurons between states may imply a common means by which cortical networks can be engaged despite brain state changes, but super-imposed on this common firing is a variability that is both specific to ongoing inputs and can be re-shaped by experience. This similarity with specifically induced variance may allow for a range of processes including perception, memory consolidation and network homeostasis. Here, we review how patterned activity in neocortical populations has been studied and what it may imply for a cortex that must be both static and plastic. This article is part of the Theo Murphy meeting issue ‘Memory reactivation: replaying events past, present and future’.

scholarly journals Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin Grieb ◽  
Sivaranjan Uppala ◽  
Gal Sapir ◽  
David Shaul ◽  
J. Moshe Gomori ◽  
...  
Keyword(s):  
Action Potential ◽  
Atp Synthase ◽  
Neural Activity ◽  
Pyruvate Dehydrogenase ◽  
Cerebral Metabolism ◽  
Neuronal Firing ◽  
Action Potential Generation ◽  
Potential Generation ◽  
Drastic Increase ◽  
Rat Cerebrum

AbstractDirect and real-time monitoring of cerebral metabolism exploiting the drastic increase in sensitivity of hyperpolarized 13C-labeled metabolites holds the potential to report on neural activity via in-cell metabolic indicators. Here, we followed the metabolic consequences of curbing action potential generation and ATP-synthase in rat cerebrum slices, induced by tetrodotoxin and oligomycin, respectively. The results suggest that pyruvate dehydrogenase (PDH) activity in the cerebrum is 4.4-fold higher when neuronal firing is unperturbed. The PDH activity was 7.4-fold reduced in the presence of oligomycin, and served as a pharmacological control for testing the ability to determine changes to PDH activity in viable cerebrum slices. These findings may open a path towards utilization of PDH activity, observed by magnetic resonance of hyperpolarized 13C-labeled pyruvate, as a reporter of neural activity.

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