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Observing hidden neuronal states in experiments
Dmitry Amakhin1, Anton Chizhov2, Guillaume Girier3
1Laboratory of Molecular Mechanisms of Neural Interactions, Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg, Russia.
Plos Computational Biology
|December 8, 2025
Summary
This study presents a new experimental method to map neuron electrical activity, revealing hidden states and validating computational models. This technique enhances our understanding of neuronal dynamics and aids in developing new control strategies.
Area of Science:
- Neuroscience
- Computational Biology
- Electrophysiology
Background:
- Electrophysiologically active cells exhibit complex dynamics crucial for neural function.
- Understanding neuronal steady states and bifurcations is key to modeling brain activity.
- Existing methods often struggle to access hidden dynamical states in neurons.
Purpose of the Study:
- To develop a general experimental protocol for constructing steady-state bifurcation diagrams in electrophysiologically active cells.
- To validate computational models by exploring previously inaccessible regions of neuronal phase space.
- To experimentally verify the slow-fast dissection method in neuronal modeling.
Main Methods:
- Utilizing a voltage-clamp protocol as a closed-loop system to inform a subsequent current-clamp protocol on the same neuron.
- Employing a slowly ramped voltage-clamp to identify stable and unstable steady states.
- Analyzing transitions between steady and spiking states in the current-clamp phase.
Main Results:
- Demonstrated a method to experimentally determine steady-state bifurcation diagrams for entorhinal cortex neurons (excitatory and inhibitory).
- Validated the ability of the voltage-clamp to predict hidden steady states observed in current-clamp.
- Provided experimental support for the slow-fast dissection method in analyzing neuronal models.
Conclusions:
- The developed protocol enables model-independent construction of bifurcation diagrams, expanding model validation capabilities.
- This technique allows for the observation of complex hidden neuronal states.
- The approach facilitates precise control of neuronal behavior beyond traditional pharmacological methods.
