Synaptic Activation of a Detailed Purkinje Cell Model Predicts Voltage-Dependent Control of Burst-Pause Responses in...

The dendritic processing in cerebellar Purkinje cells (PCs), which integrate synaptic inputs coming from hundreds of thousands granule cells and molecular layer interneurons, is still unclear. Here we have tested a leading hypothesis maintaining that the significant PC output code is represented by burst-pause responses (BPRs), by simulating PC responses in a biophysically detailed model that allowed to systematically explore a broad range of input patterns. BPRs were generated by input bursts and were more prominent in Zebrin positive than Zebrin negative (Z+ and Z-) PCs. Different combinations of parallel fiber and molecular layer interneuron synapses explained type I, II and III responses observed in vivo. BPRs were generated intrinsically by Ca-dependent K channel activation in the somato-dendritic compartment and the pause was reinforced by molecular layer interneuron inhibition. BPRs faithfully reported the duration and intensity of synaptic inputs, such that synaptic conductance tuned the number of spikes and release probability tuned their regularity in the millisecond range. Interestingly, the burst and pause of BPRs depended on the stimulated dendritic zone reflecting the different input conductance and local engagement of voltage-dependent channels. Multiple local inputs combined their actions generating complex spatio-temporal patterns of dendritic activity and BPRs. Thus, local control of intrinsic dendritic mechanisms by synaptic inputs emerges as a fundamental PC property in activity regimens characterized by bursting inputs from granular and molecular layer neurons.