Related Experiment Video

Updated: May 22, 2025

Real-time Electrophysiology: Using Closed-loop Protocols to Probe Neuronal Dynamics and Beyond
08:08

Real-time Electrophysiology: Using Closed-loop Protocols to Probe Neuronal Dynamics and Beyond

Published on: June 24, 2015

11.4K

Dynamics and conditions for inhibitory synaptic current to induce bursting and spreading depolarization in pyramidal

Hongtao Hua1,2, Huaguang Gu3, Kaihua Ma4

  • 1School of Mathematics and Science, Henan Institute of Science and Technology, Xinxiang, 453003, China.

Scientific Reports
|March 15, 2025
PubMed

Insights

Enhanced inhibitory neuron activity can paradoxically trigger mixed-mode bursting (MMB) and spreading depolarization (SD) waves, offering new insights into brain diseases like migraine and seizure.

Area of Science:

  • Computational Neuroscience
  • Neurophysiology
  • Theoretical Biology

Background:

  • Enhanced inhibitory neuron activity is typically used to suppress pyramidal neuron activity for treating brain diseases.
  • Recent experiments show this enhanced inhibition can paradoxically induce mixed-mode bursting (MMB) in pyramidal neurons, linked to migraine and seizure.
  • MMB involves high membrane potential and extracellular potassium ([K+]o), potentially leading to spreading depolarization (SD) waves.

Purpose of the Study:

  • To investigate the dynamics and conditions for MMB and SD waves evoked by enhanced inhibitory synaptic current using a theoretical model.
  • To identify novel mechanisms and thresholds for MMB induction.
  • To explore potential therapeutic strategies by understanding factors that promote or prevent MMB.

Main Methods:

  • Development of a theoretical model of a spiking pyramidal neuron.
  • Analysis of neuron dynamics under varying levels of inhibitory stimulation and extracellular potassium ([K+]o).
  • Utilized coupling and network models to simulate interactions between neurons and assess MMB propagation.

Main Results:

  • A novel negative threshold for MMB induction was identified, occurring at low [K+]o, distinct from the known positive threshold.
  • Enhanced inhibitory stimulation initially silences spiking via saddle-node bifurcation, then triggers MMB by crossing the negative threshold.
  • Coupled and network models confirmed that enhanced inhibitory effects, interneuron spiking, pyramidal neuron spiking, and inhibitory synapse conductance favor MMB, which can induce SD waves.

Conclusions:

  • This study provides a novel theoretical explanation for MMB/SD waves induced by enhanced inhibitory activity.
  • Highlights the counterintuitive role of inhibitory interneurons in potentially driving hyperexcitability.
  • Suggests that reducing specific inhibitory activities or parameters could be a potential therapeutic strategy for MMB-related diseases.
Keywords:
BifurcationBurstingInhibitory interneuronMigraineNegative thresholdSpreading depolarization

More Related Videos

Slice Patch Clamp Technique for Analyzing Learning-Induced Plasticity11:56

Slice Patch Clamp Technique for Analyzing Learning-Induced Plasticity

Published on: November 11, 2017

15.2K
Electrophysiological and Morphological Characterization of Neuronal Microcircuits in Acute Brain Slices Using Paired Patch-Clamp Recordings10:24

Electrophysiological and Morphological Characterization of Neuronal Microcircuits in Acute Brain Slices Using Paired Patch-Clamp Recordings

Published on: January 10, 2015

17.2K

Related Concept Videos

The Role of Ion Channels in Neuronal Computation01:19

The Role of Ion Channels in Neuronal Computation

A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
3.1K
Excitatory and Inhibitory Effects of Neurotransmitters01:29

Excitatory and Inhibitory Effects of Neurotransmitters

When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of...
9.6K
Integration of Synaptic Events01:28

Integration of Synaptic Events

Synaptic integration mainly includes the summation of graded potentials. Graded potentials, regardless of their type, cause subtle alterations in membrane voltage, resulting in either depolarization or hyperpolarization. These incremental changes, when combined or summed, can propel the neuron toward its threshold. Consider, for example, a membrane experiencing a +15 mV shift, causing it to depolarize from -70 mV to -55 mV. In this scenario, graded potentials govern the membrane's ability...
1.4K
Graded Potential01:19

Graded Potential

Graded potentials are localized fluctuations in the cell membrane's electrical charge, commonly found in the dendrites of neurons. The magnitude of these potential changes depends on the strength of the initiating stimulus. In a membrane at its resting potential, a graded potential signifies a voltage shift either above -70 mV or below -70 mV.
Graded potentials fall into two categories: depolarizing and hyperpolarizing. Depolarizing graded potentials typically occur when sodium (Na+) or...
3.5K
Action Potential01:31

Action Potential

Neurons communicate by firing action potentials—the electrochemical signal that is propagated along the axon. The signal results in the release of neurotransmitters at axon terminals, thereby transmitting information to the nervous system. An action potential is a specific "all-or-none" change in membrane potential that results in a rapid spike in voltage.
Membrane potential in neurons
Neurons typically have a resting membrane potential of about -70 millivolts (mV). When they...
7.6K
Postsynaptic Potential (PSP)01:32

Postsynaptic Potential (PSP)

Postsynaptic potential (PSP) refers to a change in the electrical potential of a neuron when neurotransmitters released by presynaptic neurons bind to postsynaptic receptors. This potential can either be excitatory, leading to depolarization and ultimately action potential generation, or inhibitory, leading to hyperpolarization and suppression of the postsynaptic neuron.
There are two types of receptors: ionotropic and metabotropic.
The ionotropic receptor is the membrane protein that has an...
2.2K