Long-Term Reconfiguration of Dynamic Polarization and Action Potential Initiation in Purkinje Cell Axons

Abstract

Ramon y Cajal seminally predicted ''the law of dynamic polarization of the neuron'': synaptic inputs are integrated in the dendrites and soma, which are transformed into action potentials (APs) at the axon initial segment, faithfully propagating to the axon terminal for outputs toward target neurons. However, the exceedingly small size of axons and terminals in central neurons has hindered complete validation of this unidirectional signaling scheme. Here, using cutting-edge genetically-encoded fluorescent voltage imaging, complemented by tour-de-force axonal patch-clamp recordings, I show that the traditional one-way neuronal computation exhibits dynamic, activity-dependent long-term plasticity. In cerebellar Purkinje cells, AP firing, typically initiating near the soma, drastically shifts toward various sites of initiation in axons for more than two days, following the chemical induction of learning-related dendritic long-term postsynaptic plasticity. The dynamic shift of AP initiation is accompanied by enhanced GABAA receptor activity and increased membrane excitability in the axon terminals. Thus, dendritic postsynaptic plasticity induces sustained axonal plasticity, giving rise to the emergence of local input-output elements at multiple terminals, which occasionally function as partially independent computation units. Together, the present study reveals an unprecedented dynamic modulation of neuronal processing, revolutionizing neuronal circuit computation.