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Updated: May 28, 2026

Induction of an Isoelectric Brain State to Investigate the Impact of Endogenous Synaptic Activity on Neuronal Excitability In Vivo
Published on: March 31, 2016
Spark or Sound: How Two Differing Explanatory Strategies Impact the Debate on the Physical Nature of Neuronal
Benjamin Drukarch1, Micha M M Wilhelmus1
1Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.
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Neuronal excitability manifests itself mainly in the form of non-linear, self-regenerative waves of electricity moving along the surface of neuronal axons. These waves are commonly known as action potentials (APs). Theoretical and experimental investigations of the physical and functional characteristics of APs have broadly followed along the lines of the ionic hypothesis and the associated mathematical model introduced by Hodgkin and Huxley (HH). In the current form of this bioelectrical framework, adopted in mainstream physiology and other biological sciences, the axonal membrane is conceptualized as an electronic circuit where electric current is generated and propelled as a result of the time-dependent opening and closure of voltage-operated ion channel proteins, allowing passive flow of specific ions across and along the membrane, powered by their respective electrochemical gradients. Although representing mainstream research, the bioelectric perspective has been criticized for its narrow focus on the electrical characteristics of APs, whilst ignoring other physical manifestations of the nerve signal, particularly mechanical and thermal changes coinciding with AP propagation. As an alternative, a macroscopic thermodynamics-based acoustic theory has been outlined, in which all electric and non-electric manifestations of the nerve signal are considered as a result of a single density pulse in the axonal membrane carried by a reversible lipid membrane phase transition and momentum conservation. Representing a minority view, however, this unified, acoustic perspective on the physical nature of neuronal excitability is largely ignored by representatives of the bioelectric perspective. Here, we draw special attention to the philosophical dimension of the communication failure between the two communities of scientists. We argue that adherents of the bioelectric perspective favor a mechanist type of explanation, whilst supporters of the acoustic perspective are committed to so-called covering-law types of explanation. We conclude that it is this thus far unrecognized philosophical rift, rather than specific scientific differences in opinion, that blocks fruitful interdisciplinary cooperation necessary for building a comprehensive, fully integrated notion of the physical nature of neuronal excitability. Suggestions of how to bridge this conceptual gap are formulated.
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