The role of synaptic and voltage-gated currents in the control of Purkinje cell spiking: a modeling study.
We have used a realistic computer model to examine interactions between synaptic and intrinsic voltage-gated currents during somatic spiking in cerebellar Purkinje cells. We have shown previously that this model generates realistic in vivo patterns of somatic spiking in the presence of continuous background excitatory and inhibitory input (). In the present study, we analyzed the flow of synaptic and intrinsic currents across the dendritic membrane and the interaction between the soma and dendrite underlying this spiking behavior. This analysis revealed that: (1) dendritic inward current flow was dominated by a noninactivating P-type calcium current, resulting in a continuous level of depolarization; (2) the mean level of this depolarization was controlled by the mean rate of excitatory and inhibitory synaptic input; (3) the synaptic control involved a voltage-clamping mechanism exerted by changes of synaptic driving force at different membrane potentials; (4) the resulting total current through excitatory and inhibitory synapses was near-zero, with a small outward bias opposing the P-type calcium current; (5) overall, the dendrite acted as a variable current sink with respect to the soma, slowing down intrinsic inward currents in the soma; (6) the somato-dendritic current showed important phasic changes during each spike cycle; and (7) the precise timing of somatic spikes was the result of complex interactions between somatic and dendritic currents that did not directly reflect the timing of synaptic input. These modeling results suggest that Purkinje cells act quite differently from simple summation devices, as has been assumed previously in most models of cerebellar function. Specific physiologically testable predictions are discussed.
Jaeger
D
D
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
De Schutter
E
E
Bower
J M
JM
D000200:Action Potentials; D000818:Animals; D004553:Electric Conductivity; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D008959:Models, Neurological; D011689:Purkinje Cells / Q000502:physiology*; D013569:Synapses / Q000502:physiology*