These sets of models were used to investigate the mechanisms behind the large depolarization baseline offset (DBLO) seen in CA1 pyramidal neurons. Somatic step-current injection is commonly used to characterize electrophysiological properties of neurons. Many neuronal types show a large depolarization baseline offset (DBLO), which is defined as the positive difference between the minimum membrane potential during action potential trains and resting. We used stochastic parameter search in conductance-based models to show that four key factors together account for high DBLO: Liquid Junction Potential correction, high backpropagating passive charges during the repolarization phase of an action potential, fast potassium delayed rectifier kinetics, and appropriate transient sodium current kinetics. Several plausible mechanisms for DBLO, such as Ohmic depolarization due to current input or low-pass filtering by the membrane, fail to explain the effect, and many published sophisticated conductance-based models do not correctly manifest high DBLO. Finally, models with experimentally consistent levels of DBLO constrain the parameter space of ion channel levels and kinetics. We also highlight the role these models may play in correctly identifying neuronal factors behind several cellular mechanisms such as bistable firing, spikelets, and calcium influx.
Experimental motivation: Single compartment models and ball-and-stick models fitted to whole-cell patch clamp data. Base kinetics from previously published experimental and simulation studies.
Model Type: Channel/Receptor; Neuron or other electrically excitable cell
Region(s) or Organism(s): Hippocampus; Mouse
Cell Type(s): Hippocampus CA1 pyramidal GLU cell
Currents: I Calcium; I K; I Na,p; I Na,t; I Potassium; I Sodium; I h
Receptors:
Genes:
Transmitters:
Model Concept(s): Action Potentials; Axonal Action Potentials; Calcium dynamics; Conductances estimation; Impedance; Ion Channel Kinetics; Methods; Parameter Fitting; Simplified Models
Simulation Environment: MOOSE/PyMOOSE; NEURON
Implementer(s): Kumar, Anal
References:
Kumar A, Shahul AK, Bhalla US. (2025). Mechanisms and implications of high depolarization baseline offsets in conductance-based neuronal models. Journal of neurophysiology. [PubMed]