Séminaire du CIMMUL | Nooshin Abdollahi

Axonal excitability: Importance of intrinsic properties and extracellular current flow revealed by computational modeling

Nooshin Abdollahi
Étudiante au doctorat
University of Toronto

Résumé

Neurons rely on axons to transmit information over long distances via action potentials, or spikes (digital signals). Despite the squid giant axon being used for some of the seminal experiments that are the foundation of our understanding of neuronal excitability, axon excitability is understudied compared to excitability in other parts of the neuron, such as the soma or dendrites, which are more amenable to electrophysiological recordings. Using optogenetics and computational modeling, we discovered that the axon behaves as a high-pass filter by selectively responding to intense and abrupt depolarizing input because of the negative feedback mediated by specific type of potassium channels. This “design” helps ensure reliable spike propagation. How do axons respond when subjected to repeated depolarizing stimuli at various frequencies? Axonal spiking also depends on the refractory properties of the axon. By reproducing experimental data in a mathematical model, fitted parameter values reveal the multiphasic changes in post-spike excitability. I will explain how heterogeneity in these properties leads to asynchronous spiking at high stimulus frequencies.

The above phenomena depend on the flow of current onto and through the axon membrane, but a compete explanation of spike propagation requires consideration of current flow inside and outside the axon. For instance, intracellular axial current flow (and its dependence on axon diameter) affects the speed of spike propagation. Extracellular current flow is also important but the extracellular space is typically modeled as being connected to ground, resulting in infinite extracellular conductivity; in many cases (including in intact nerve), that assumption is invalid. By extension, transmembrane voltage is often calculated under the assumption that extracellular voltage is zero, but this too is inaccurate. By simulating the axonal extracellular conditions and tracking the flow of current intracellularly and extracellularly, we found that axons with the same intrinsic properties facing different extracellular conditions propagate spikes at different conduction velocities. Moreover, this effect interacts with intrinsic axon properties, meaning certain intrinsic factors like myelin thickness can have a large or small effect on velocity depending on the extracellular resistivity.

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Le séminaire aura lieu au local 3820 du pavillon Alexandre-Vachon et en ligne.

Pour rejoindre la réunion Zoom :
https://ulaval.zoom.us/j/62680136430?pwd=eldBYjdNTG5QR2VxTTFqbVM4UGVRZz09

Meeting ID: 626 8013 6430
Passcode: 693150