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The role of synaptic and voltage-gated currents in the control of Purkinje cell spiking: a modeling study.

D. Jaeger, E. De Schutter, J.M. Bower


The Journal of Neuroscience 17:91-106 (1997)

Abstract - 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 previously shown that this model generates realistic in vivo patterns of somatic spiking in the presence of continuous background excitatory and inhibitory input (De Schutter & Bower 1994b). 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 non-inactivating 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 background 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 previously been assumed in most models of cerebellar function. Specific physiologically testable predictions are discussed. The dendritic trees of single cerebellar Purkinje cells receive about 175,000 excitatory glutamatergic inputs from granule cells in the rat (Napper & Harvey 1988b), and about 1,500 GABAA inputs from local interneurons (Korbo, Andersen, et al. 1993, Sultan, Ellisman, et al. 1995). Clearly, this large number of inputs suggests that the synaptic control of somatic spiking in Purkinje cells could be quite complex. In addition, Purkinje cell dendrites are also known to have substantial dendritic voltage gated calcium curents and calcium-activated potassium currents (Llinás, Nicholson, et al. 1968, Llinás & Sugimori 1980b, Gruol, Dionne, et al. 1989, Usowicz, Sugimori, et al. 1992), which strongly influence membrane potential (Llinás & Sugimori 1980b, Llinás & Sugimori 1992), and can be activated by synaptic input (Eilers, Augustine, et al. 1995). One function of the activation of calcium currents with synaptic input may be the amplification of small synchronous synaptic inputs (De Schutter & Bower 1994c). It is still unclear, however, what pattern of current flow underlies the typical fast spontaneous spiking activity of 10 to 100 Hz of Purkinje cells recorded in vivo (Bower & Woolston 1983). Due to the large number of synaptic inputs it seems likely that Purkinje cells in vivo receive an ongoing baseline of synaptic activity. Such a pattern of many asynchronous synaptic inputs successfully reproduced the in vivo spike pattern in a realistic Purkinje cell model (De Schutter & Bower 1994b). The objective of the present study was to use the realistic Purkinje cell model to examine the pattern of synaptic and voltage-gated dendritic currents that produces ongoing somatic spiking. We applied several new analysis techniques to examine this issue. We find that in the model intrinsic dendritic currents strongly influenced the time course of dendritic membrane potential. As a consequence, the timing of somatic spikes did not reflect the timing of particular synaptic inputs. The common assumption in cerebellar network models that Purkinje cell spiking reflects a simple summation of inputs (Marr 1969, Albus 1971, Fujita 1982, Kanerva 1988) may therefore not hold. Our predictions are readily testable through specific experiments. If experimentally confirmed, our modeling predictions have important consequences for theories of cerebellar function.