Understanding the Scope of the Contemporary Controversy about the Physical Nature and Modeling of the Action Potential: Insights from History and Philosophy of (Neuro)Science

According to mainstream neuroscience, the action potential (AP) is a purely dissipative electrical phenomenon that should be modeled as such. However, also (essentially) reversible mechanical, thermal, and optical changes in the neuron have been reported to accompany the movement of the AP along the axonal surface. These are not accounted for in the prevailing (bio)-electric theory of neuronal excitability, originally introduced by Hodgkin and Huxley (HH) and mathematically formulated in their famous HH model of the AP. An alternative theory and model of the AP has been developed recently by the membrane biophysicists Heimburg and Jackson (HJ). Based on the laws of macroscopic thermodynamics, in the HJ model, the AP is treated as a compression wave propagating in the axonal surface membrane, similar to the movement of acoustic pulses in a material. Predicting both electrical and non-electrical manifestations of the AP to result from a reversible lipid phase transition in the axonal membrane, the HJ model explains neuronal excitability as an electromechanical process driven by the thermodynamic properties of the lipid membrane. Promising to provide a complete representation of the AP phenomenon, the introduction of the HJ model was heralded by some as a (potential) revolution in neuroscience but was largely dismissed by mainstream neuroscience. Applying Kuhn’s well-known philosophical analysis of paradigm shifts in science and Giere’s theory of perspectival realism to the case, we here argue that, instead of a competition for truth between the HH and HJ models, chances for further development and evaluation of the thermodynamic theory as a comprehensive explanation of the AP is better served by considering the controversy in terms of an interaction between two incompatible but valid scientific perspectives. In our opinion, doing so will provide a fruitful theoretical basis for experimental efforts to improve the explanatory understanding of the physical nature of neuronal signaling.