Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

Abstract

The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na ⁺ channel inactivation, resulting in a marked reduction in overlap of the inward Na ⁺, and outward K ⁺, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na ⁺ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37–42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code.

Author Summary

Conserving energy is essential to life. The brain, while only 2% of the body mass, uses an astounding 20% of its energy. It has long been assumed that this large energy consumption was due to the need to generate the electrical signals through which brain cells communicate: the action potentials. However, recent results reveal that the wires of the mammalian brain – the axons – are remarkably energy efficient. How is this energy efficiency obtained? Here we addressed this question by performing recordings and computational models of mammalian brain cells. We found that the increase in body temperature associated with the evolution of warm-blooded animals had an energetic benefit. The action potentials of warm-blooded animals became remarkably energy efficient, owing simply to the increase in body temperature. These results indicate that mammalian brains, although requiring a great deal of energy to operate, are actually more efficient than expected.