Mitochondria delay action potential propagation

The internal resistance of axons to ionic current flow determines action potential conduction velocity. Although mitochondria support axonal function, axons have been modeled as organelle-free cables, and mitochondrial impact on conduction velocity, specifically by increasing internal resistance, remains understudied. We combine computational modeling and electron microscopy of forebrain premotor axons controlling birdsong production. Modeling shows that when the propagating action potential in an unmyelinated axon encounters a mitochondrion, conduction velocity decreases, delaying the action potential by tenths of microseconds to microseconds, an effect that is stronger in small axons. Axonal mitochondria thereby induce conduction inhomogeneities, accumulating total delays of tenths of milliseconds to ~ a millisecond over 3 millimeters-long axons, in the range of the temporal precision of these neurons. Thus, by partially occupying the axoplasm, mitochondria constrain information processing in vertebrate small-diameter axons. Our model should permit future investigations on the impact of mitochondrial axonal plasticity on action potential temporal coding.