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Biophysics of wiring the brain

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Action Potentials are typically used by axons to transmit information rapidly and reliably. Yet, the reliability of transmission along fibers below 0.5 micrometer diameter, such as cortical collateral and cerebellar axons, is unkown.

I will show how conduction along such thin axons is affected by the probabilistic nature of voltage-gated ion channels mediating the spike. I address this problem using biophysically realistic stochastic simulations and modelling up to a million individual ion channels.

The three key findings are that fluctuations in single Na channels set a general lower limit to unmyelinated axon diameter at 0.1 micrometer. This limit operates above other biophysical limits to axon diameter and matches the smallest known axons across the animal kingdom. In axons below 0.5 micrometer, such as the average pyramidal cell collateral and parallel fibers in cerebellum, channel noise introduces history-dependent spike time jitter in the order of milliseconds.Reliability decreases the further action potentials have to travel and channel noise produces a novel mode of action potential propagation: stochastic micro-saltatory conduction. Finally axonal channel noise causes variability of the action potential wave form – which could partially explain fluctuations in transmitter release at central synapses, innervated typically by thin axons.

In conclusion, these findings will be related to noise constraints on neural coding to cell design and allow prediction of cortical circuit anatomy.

This talk is part of the Craik Club series.

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