Coordinated regulation of timing and strength of synaptic outputs by adrenergic receptors through control of action potentials in Purkinje cells

In contrast to conventional view about the faithful signaling in neuronal axons by all-or-none action potentials, recent studies have shown that axons exhibit dynamic change in action potential waveforms and/or conduction velocities in a manner dependent on neuronal activity and/or inputs to axonal compartments from other neurons. It was recently shown that a well-known second messenger cAMP negatively regulates the axonal voltage-gated Na + channels, which decreases the amplitude and conduction velocity of action potentials in axons of cerebellar Purkinje cells. To understand the signaling mechanism and physiological context of the cAMP-mediated action potential modulation, we studied the involvement of one of neuromodulators, adrenergic system, using direct patch-clamp recordings from axons and/or terminals of Purkinje cells. We demonstrate that Purkinje cell axons exhibit negative control of action potentials in amplitude and conduction velocity by β-adrenergic receptors in a manner dependent on the axonal length through specific reduction of axonal Na + currents. On the other hand, β-adrenergic receptors increased presynaptic release probability without changing the amount of readily releasable vesicles in axon terminals of Purkinje cells. Together, our data highlight a physiological pathway to activate cAMP signaling to cause the axonal length-dependent dynamic changes in the timing and strength of synaptic transmission.