Synaptic control of spiking in cerebellar Purkinje cells: Dynamic current clamp based on model conductances

Previous simulations using a realistic model of a cerebellar Purkinje cell suggested that synaptic control of somatic spiking in this cell type is med iated by voltage-gated intrinsic conductances and that inhibitory rather th an excitatory synaptic inputs are more influential in controlling spike tim ing. In this paper, we have tested these predictions physiologically using dynamic current clamping to apply model-derived synaptic conductances to Pu rkinje cells in vitro. As predicted by the model, this input transformed th e in vitro pattern of spiking into a different spike pattern typically obse rved in vivo. A net inhibitory synaptic current was required to achieve suc h spiking, indicating the presence of strong intrinsic depolarizing current s. Spike-triggered averaging confirmed that the length of individual interv als between spikes was correlated to the amplitude of the inhibitory conduc tance but was not influenced by excitatory inputs. Through repeated present ation of identical stimuli, we determined that the output spike rate was ve ry sensitive to the relative balance of excitation and inhibition in the in put conductances. In contrast, the accuracy of spike timing was dependent o n input amplitude and was independent of spike rate. Thus, information coul d be encoded in Purkinje cell spiking in a precise spike time code and a ra te code at the same time. We conclude that Purkinje cell responses to synap tic input are strongly dependent on active somatic and dendritic properties and that theories of cerebellar function likely need to incorporate single -cell dynamics to a greater degree than is customary.