A Thermodynamic Interpretation of the Stimulated Raman Spectroscopic Signature of an Action Potential in a Single Neuron

Abstract

It has previously been suggested that the plasma membrane condenses and melts reversibly during an action potential in a neuron. If true it has fundamental consequences for our understanding of the regulation of biological functions during an action potential. It has long been known that the electrical dipoles in the neuronal membrane reorient during an action potential, observed through a variety of optical methods. However, this information has been insufficient to confirm if and how the collective thermodynamic state of the neuronal membrane changes during an action potential. Here, we show that hyperspectral stimulated Raman spectroscopy can resolve the thermodynamic state of the neuronal membranes in a single neuron during an action potential. Based on these measurements we provide the first evidence that the system condenses during the de-polarisation phase and melts during the polarisation phase. Statement of SignificanceWhile action-potentials can be measured using a variety of methods, none of these methods have been able to provide sufficient information to characterise the collective thermodynamic state of the membrane during an action-potential. Therefore, new tools are required to satisfactorily resolve the fundamental nature of the phenomenon, i.e. does the wave-front propagates irreversibly/diffusively as in the burning of a fuse, or reversibly/elastically as in the propagation of sound. It has been postulated that if action-potentials indeed propagate elastically, then the membrane must undergo a localised condensation during the actionpotential. This article confirms and quantifies the condensation of the membrane during an action-potential based on time-resolved changes in the Raman band at 2930 cm -1 , also known as the "melting-marker".

Shock and detonation waves at an interface and the collision of action potentials

“…Indeed, Tasaki has measured changes in the emission spectra of solvatochromic dyes in nerves during an action potential and he showed that the spectral width decreases (Tasaki et al, 1973), and hence it can now be claimed the membrane stiffness increases during an action potential per eq.17. Recently, an attempt was made to perform similar measurements based in changes in the Raman spectra of single neurons (Shrivastava et al, 2020). Similar measurements under a range of physico-chemical conditions and excitable systems, as outlined by others (Fillafer et al, 2019;Fillafer and Schneider, 2015;Wang et al, 2018), will lead to the required clarity on the mechanisms of nerve pulse propagation.…”

Shock and Detonation Waves at an Interface and the Collision of Action Potentials

“…Given that the evidence of a increased order and compression was recently presented for an action potential in a single neuron (55), and an undisputable role of mechanics in neuronal signal transduction (56), the physical insights provided by the above mechanism for collision need to be investigated during the collision or interaction of waves in neurons. In general, excitation waves from propagating graded potentials to action-potential, show an entire range of interactions; from superposition to supra-linear, to sublinear summation (57).…”