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Computational analysis of a 9D model for a small DRG neuron.
Parul Verma1, Achim Kienle2,3, Dietrich Flockerzi2,3
1Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, USA.
Journal of Computational Neuroscience
|August 31, 2020
Summary
This study uses numerical bifurcation analysis to explore the dynamics of a small dorsal root ganglion (DRG) neuron model, revealing how ion channel conductances influence pain signaling. Findings show parameter changes can shift neuron behavior between stable states, action potentials, and complex oscillations, offering insights into pain mechanisms.
Area of Science:
- Neuroscience
- Computational Biology
- Biophysics
Background:
- Small dorsal root ganglion (DRG) neurons are key nociceptors responsible for pain sensation.
- Understanding DRG neuron dynamics is crucial for pain research and therapeutic development.
Purpose of the Study:
- To perform a numerical bifurcation analysis of a Hodgkin-Huxley type DRG neuron model.
- To investigate the influence of maximal ion channel conductances and external current on neuron dynamics.
- To identify and characterize different dynamical regimes, including stable states, action potentials, and mixed-mode oscillations (MMOs).
Main Methods:
- Utilized a 9-state variable Hodgkin-Huxley model incorporating Nav1.7, Nav1.8, leak, delayed rectifier potassium, and A-type transient potassium channels.
- Conducted numerical bifurcation analysis by varying maximal conductances (particularly Nav1.8) and external current.
- Analyzed transitions between dynamical regimes and characterized MMOs, including complex concatenated patterns and potential chaotic behavior.
Main Results:
- Neuron dynamics are most sensitive to the Nav1.8 channel maximal conductance.
- Identified parameter regions exhibiting stable steady states, periodic action potential firing, MMOs, and bistability.
- Detailed the emergence and evolution of MMOs as external current decreases, including sequences of large action potentials with increasing numbers of small peaks and complex concatenated patterns.
- Observed small windows of aperiodic, potentially chaotic, oscillations.
Conclusions:
- Bifurcation analysis reveals diverse dynamical patterns in DRG neuron models regulated by ion channel parameters and external current.
- These dynamical patterns, including repetitive firing and MMOs, have potential translational significance for understanding and investigating pain mechanisms.
- Manipulating these parameters could offer novel approaches for pain research and intervention.
