Impact of frequency on the energetic efficiency of action potentials

Sodium entry during the decaying phase of the action potential determines the metabolic efficiency of a neuron's spiking mechanism. Recent studies have reported that mammalian action potentials are close to metabolic optimality but that fast-spiking inhibitory neurons are less efficient than their pyramidal counterparts. It is postulated that this represents nature's tradeoff between metabolic efficiency and the ability to discharge at high rates. Using eight different published Hodgkin-Huxley models of mammalian neurons to cover a wide range of action potential metabolic efficiencies, we show that the cost of operating a neuron is heavily dependent on its output frequency. We observe that this cost is significantly smaller than the frequency-dependent cost naively estimated from an isolated action potential, the gap increasing with increasing frequencies. Our results demonstrate that metabolic efficiency cannot be considered only in terms of isolated action potentials but must be studied over a range of meaningful frequencies.