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

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 Significance While 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 action-potential. 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”.