A unified model of CA1/3 pyramidal cells: an investigation into excitability.
After-depolarisation is a hallmark of excitability in hippocampal pyramidal cells of CA1 and CA3 regions, because it constitutes the subthreshold relation between inward and outward ionic currents. This relationship determines the nominal response to stimuli and provides the necessary conditions for firing a spike or a burst of action potentials. Nevertheless, after-depolarisation is an inherently transient phenomenon that is not very well understood. We study after-depolarisation using a single-compartment pyramidal-cell model based on recent voltage- and current-clamp experimental data. We systematically investigate CA1 and CA3 behaviour and show that changes to maximal conductances of T-type Ca(2+)-current and muscarinic-sensitive and delayed rectifier K(+)-currents are sufficient to switch the behaviour of the model from a CA3 to a CA1 neuron. We use model analysis to define after-depolarisation and bursting threshold. We also explain the influence of particular ionic currents on this phenomenon. This study ends with a sensitivity analysis that demonstrates the influence of specific currents on excitability. Counter-intuitively, we find that a decrease of Na(+)-current could cause an increase in excitability. Our analysis suggests that a change of high-voltage activated Ca(2+)-current can have a similar effect.
Nowacki
Jakub
J
Bristol Centre for Applied Nonlinear Mathematics, Department of Engineering Mathematics, University of Bristol, Queen's Building, University Walk, Bristol BS8 1TR, UK.
Osinga
Hinke M
HM
Brown
Jon T
JT
Randall
Andrew D
AD
Tsaneva-Atanasova
Krasimira
K
D000200:Action Potentials / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D056654:CA3 Region, Hippocampal / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D007700:Kinetics; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology
D015220:Calcium Channels; D015221:Potassium Channels; D015222:Sodium Channels; D000244:Adenosine Diphosphate