EXPLORING ENERGY-EFFICIENCY OF AXONAL SPIKES USING MODELS OF HIPPOCAMPAL MOSSY FIBER

Axonal spikes are a highly energy-efficient neuronal code propagating toward the presynaptic terminals. Classical study in squid giant axon showed substantial temporal overlap of Na⁺ inflow and the delayed K⁺ outflow during action potentials, and requires the extra energy to re-establish the electrochemical gradient through energy-demanding ionic pumps. In contrast, axonal action potentials in hippocampal mossy fibers were shown to be generated with a small overlap of Na⁺ inflow and K⁺ outflow, thereby saving energy demand. In this study, we calculated axonal action potentials and underlying Na⁺ and K⁺ currents with various models of hippocampal mossy fibers implemented with ionic conductance determined experimentally, from a simple ball and stick model with en passant structure, to a morphologically detailed model reconstructed from microscopic structure. Using this approach, an attempt was made to investigate activity-dependent dynamic changes in the energy demand of axonal spike signaling by quantifying the temporal overlap of Na⁺ influx and K⁺ efflux during repetitive axonal spikes. The overlaps of the currents decreased progressively with repetitive stimulation by delaying activation of K⁺ currents during the train, possibly due to accumulated inactivation of K⁺ channels. When the model of the voltage-dependent K⁺ channel was exchanged with a non-inactivating type, the use-dependent reduction of the overlap was not observed. These results suggested that the energy demand of axonal spikes is modulated by neuronal activity in an activity-dependent manner, possibly due to use-dependent accumulated inactivation of K⁺ channels.