Neurosimilator for Undergraduate Biophysics and Neurophysiology Courses.

Stringent animal welfare principles are forcing undergraduate instructors to avoid the use of animals. Therefore, many hands-on lab sessions using laboratory animals are progressively replaced by computer simulations. These versatile software simulations permit the observation of the behavior of biological systems under a great variety of experimental conditions. While this versatility is important, computer simulations often work even when a student makes wrong assumptions, a situation that poses its own pedagogical problem. Hands-on learning provides pupils with the opportunity to safely make mistakes and learn organically through trial and error and should therefore still be promoted. We propose an electronic model of an excitable cell composed of different modules representing different parts of a neuron - dendrites, soma, axon and node of Ranvier. We describe a series of experiments that allow students to better understand differences between passive and active cell responses and differences between myelinated and demyelinated axons. These circuits can also be used to demonstrate temporal and spatial summation of signals coming to the neuron via dendrites, as well as the neuron coding by firing frequency. Finally, they permit experimental determination along with theoretical calculations of important biophysical properties of excitable cells, such as rheobase, chronaxie and space constant. This open-source model has been successfully integrated into an undergraduate course of the physiology of excitable cells and student feedback assessment reveals that it helped students to understand important notions of the course. Thus, this neuromorphic circuit could be a valuable tool for biophysics and neuroscience courses in other universities.

A Minimal Model Shows that a Positive Feedback Loop Between sNHE and SLO3 can Control Mouse Sperm Capacitation.

When mammalian spermatozoa are released in the female reproductive tract, they are incapable of fertilizing the oocyte. They need a prolonged exposure to the alkaline medium of the female genital tract before their flagellum gets hyperactivated and the acrosome reaction can take place, allowing the sperm to interact with the oocyte. Ionic fluxes across the sperm membrane are involved in two essential aspects of capacitation: the increase in intracellular pH and the membrane hyperpolarization. In particular, it has been shown that the SLO3 potassium channel and the sNHE sodium-proton exchanger, two sperm-specific transmembrane proteins, are necessary for the capacitation process to occur. As the SLO3 channel is activated by an increase in intracellular pH and sNHE is activated by hyperpolarization, they act together as a positive feedback system. Mathematical modeling provides a unique tool to capture the essence of a molecular mechanism and can be used to derive insight from the existing data. We have therefore developed a theoretical model formalizing the positive feedback loop between SLO3 and sHNE in mouse epididymal sperm to see if this non-linear interaction can provide the core mechanism explaining the existence of uncapacited and capacitated states. We show that the proposed model can fully explain the switch between the uncapacitated and capacited states and also predicts the existence of a bistable behaviour. Furthermore, our model indicates that SLO3 inhibition, above a certain threshold, can be effective to completely abolish capacitation.