Metabolic cost as a unifying principle governing neuronal biophysics.

The brain contains an astonishing diversity of neurons, each expressing only one set of ion channels out of the billions of potential channel combinations. Simple organizing principles are required for us to make sense of this abundance of possibilities and wealth of related data. We suggest that energy minimization subject to functional constraints may be one such unifying principle. We compared the energy needed to produce action potentials singly and in trains for a wide range of channel densities and kinetic parameters and examined which combinations of parameters maximized spiking function while minimizing energetic cost. We confirmed these results for sodium channels using a dynamic current clamp in neocortical fast spiking interneurons. We find further evidence supporting this hypothesis in a wide range of other neurons from several species and conclude that the ion channels in these neurons minimize energy expenditure in their normal range of spiking.