Metabolic Cost of Dendritic Ca(2+) Action Potentials in Layer 5 Pyramidal Neurons

Pyramidal neurons consume most signaling-related energy to generate action potentials (APs) and perform synaptic integration. Dendritic Ca(2+) spike is an important integration mechanism for coupling inputs from different cortical layers. Our objective was to quantify the metabolic energy associated with the generation of Ca(2+) APs in the dendrites. We used morphology-based computational models to simulate the dendritic Ca(2+) spikes in layer 5 pyramidal neurons. We calculated the energy cost by converting Ca(2+) influx into the number of ATP required to restore and maintain the homeostasis of intracellular Ca(2+) concentrations. We quantified the effects of synaptic inputs, dendritic voltage, back-propagating Na(+) spikes, and Ca(2+) inactivation on Ca(2+) spike cost. We showed that much more ATP molecules were required for reversing Ca(2+) influx in the dendrites than for Na(+) ion pumping in the soma during a Ca(2+) AP. Increasing synaptic input increased the rate of dendritic depolarization and underlying Ca(2+) influx, resulting in higher ATP consumption. Depolarizing dendritic voltage resulted in the inactivation of Ca(2+) channels and reduced the ATP cost, while dendritic hyperpolarization increased the spike cost by de-inactivating Ca(2+) channels. A back-propagating Na(+) AP initiated in the soma increased Ca(2+) spike cost in the apical dendrite when it coincided with a synaptic input within a time window of several milliseconds. Increasing Ca(2+) inactivation rate reduced Ca(2+) spike cost, while slowing Ca(2+) inactivation increased the spike cost. The results revealed that the energy demand of a Ca(2+) AP was dynamically dependent on the state of dendritic activity. These findings were important for predicting the energy budget for signaling in pyramidal cells, interpreting functional imaging data, and designing energy-efficient neuromorphic devices.