DENDRITIC VOLTAGE AND CALCIUM-GATED CHANNELS AMPLIFY THE VARIABILITY OF POSTSYNAPTIC RESPONSES IN A PURKINJE-CELL MODEL

The dendrites of most neurons express several trs-pes of voltage and C a2+-gated channels. These ionic channels can be activated by subthresh old synaptic input. but the functional role of such activations in viv o is unclear. The interaction between dendritic channels and synaptic background input as it occurs in vivo was studied in a realistic compu ter model of a cerebellar Purkinje cell. II previously was shown using this model that dendritic Ca2+ channels amplify the somatic response to synchronous excitatory inputs. In this study, it is shown that dend ritic ion channels also increased the somatic membrane potential fluct uations generated by the background input. This amplification caused a highly variable somatic excitatory postsynaptic potential (EPSP) in r esponse to a synchronous excitatory input. The variability scaled with the size of the response in the model with excitable dendrite, result ing in an almost constant coefficient of variation, whereas in a passi ve model the membrane potential fluctuations simply added onto the EPS P. Although the EPSP amplitude in the active dendrite model was quite variable for different patterns of background input, it was insensitiv e to changes in the timing of the synchronous input by a few milliseco nds. This effect was explained by slow changes in dendritic excitabili ty. This excitability was determined by how the background input affec ted the dendritic membrane potentials in the preceding 10-20 ms, causi ng changes in activation of voltage and Ca2+-gated channels. The most important model variables determining the excitability at the time of a synchronous input were the Ca2+-activation of K+ chan nels and the i nhibitory synaptic conductance, although many other model variables co uld be influential for particular background patterns. Experimental ev idence for the amplification of postsynaptic variability by active den drites is discussed. The amplification of the variability of EPSPs has important functional consequences in general and for cerebellar Purki nje cells specifically. Subthreshold, background input has a much larg er effect on the responses to coherent input of neurons with active de ndrites compared with passive dendrites because it can change the effe ctive threshold for firing. This gives neurons with dendritic calcium channels an increased information processing capacity and provides the Purkinje cell with a gating function.