Ionic mechanisms of endogenous bursting in CA3 hippocampal pyramidal neurons: A model study

Research output: Contribution to journalArticle

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Abstract

A critical property of some neurons is burst firing, which in the hippocampus plays a primary role in reliable transmission of electrical signals. However, bursting may also contribute to synchronization of electrical activity in networks of neurons, a hallmark of epilepsy. Understanding the ionic mechanisms of bursting in a single neuron, and how mutations associated with epilepsy modify these mechanisms, is an important building block for understanding the emergent network behaviors. 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 fast-slow 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.

Original languageEnglish (US)
Article numbere2056
JournalPLoS One
Volume3
Issue number4
DOIs
StatePublished - Apr 30 2008
Externally publishedYes

Fingerprint

Pyramidal Cells
Neurons
Epilepsy
neurons
T-Type Calcium Channels
epilepsy
calcium
Mutation
Sodium Channels
Potassium Channels
Action Potentials
Hippocampus
Chemical activation
mutation
potassium channels
hippocampus
action potentials
Potassium
Synchronization
Sodium

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ionic mechanisms of endogenous bursting in CA3 hippocampal pyramidal neurons : A model study. / Xu, Jun; Clancy, Colleen E.

In: PLoS One, Vol. 3, No. 4, e2056, 30.04.2008.

Research output: Contribution to journalArticle

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