Ionic mechanisms of bursting in CA3 pyramidal neurons (Xu and Clancy 2008)


"... We present a single-compartment model of a CA3 hippocampal pyramidal neuron based on recent experimental data. We then use the model to determine the roles of primary depolarizing currents in burst generation. The single compartment model incorporates accurate representations of sodium (Na+) channels (NaV1.1) and T-type calcium (Ca2+) channel subtypes (CaV3.1, CaV3.2, and CaV3.3). Our simulations predict the importance of Na+ and T-type Ca2+ channels in hippocampal pyramidal cell bursting and reveal the distinct contribution of each subtype to burst morphology. We also performed fastslow analysis in a reduced comparable model, which shows that our model burst is generated as a result of the interaction of two slow variables, the T-type Ca2+ channel activation gate and the Ca2+-dependent potassium (K+) channel activation gate. The model reproduces a range of experimentally observed phenomena including afterdepolarizing potentials, spike widening at the end of the burst, and rebound. Finally, we use the model to simulate the effects of two epilepsy-linked mutations: R1648H in NaV1.1 and C456S in CaV3.2, both of which result in increased cellular excitability."

Model Type: Neuron or other electrically excitable cell

Cell Type(s): Hippocampus CA3 pyramidal GLU cell

Currents: I Na,t; I L high threshold; I N; I T low threshold; I A; I K; I M; I K,Ca; I Calcium

Receptors: GabaB

Genes: Nav1.1 SCN1A; Cav3.2 CACNA1H; Cav3.1 CACNA1G; Cav3.3 CACNA1I

Model Concept(s): Bursting; Ion Channel Kinetics

Simulation Environment: C or C++ program

References:

Xu J, Clancy CE. (2008). Ionic mechanisms of endogenous bursting in CA3 hippocampal pyramidal neurons: a model study. PloS one. 3 [PubMed]


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