Influence of spatially segregated IP 3 -producing pathways on spike generation and transmitter release in Purkinje cell axons

Significance IP3 receptors are well-documented regulators of intracellular calcium concentration, but their role in axons of central neurons remains unexplored. Here we show that IP3 receptors are present throughout the axon of cerebellar Purkinje cells where their activation leads to calcium release from intracellular stores. We reveal distinct, sharply delimited signaling cascades leading to IP3 production in the axon initial segment (AIS), in the more distal part of the axon, and in synaptic terminals. In the AIS, IP3 -induced calcium rises inhibit action potential generation, whereas similar signals in axonal terminals increase transmitter release. Metabotropic purinergic receptors appear to control the IP3 -driven cascade. Altogether, the results reveal potent actions of IP3 in central axons, which are both diverse and spatially constrained.