Beyond faithful conduction: Short-term dynamics, neuromodulation, and long-term regulation of spike propagation in the axon

Abstract

Most spiking neurons are divided into functional compartments: a dendritic input region, a soma, a site of action potential initiation, an axon trunk and its collaterals for propagation of action potentials, and distal arborizations and terminals carrying the output synapses. The axon trunk and lower order branches are probably the most neglected and are often assumed to do nothing more than faithfully conducting action potentials. Nevertheless, there are numerous reports of complex membrane properties in non-synaptic axonal regions, owing to the presence of a multitude of different ion channels. Many different types of sodium and potassium channels have been described in axons, as well as calcium transients and hyperpolarization-activated inward currents. The complex time- and voltage-dependence resulting from the properties of ion channels can lead to activity-dependent changes in spike shape and resting potential, affecting the temporal fidelity of spike conduction. Neural coding can be altered by activity-dependent changes in conduction velocity, spike failures, and ectopic spike initiation. This is true under normal physiological conditions, and relevant for a number of neuropathies that lead to abnormal excitability. In addition, a growing number of studies show that the axon trunk can express receptors to glutamate, GABA, acetylcholine or biogenic amines, changing the relative contribution of some channels to axonal excitability and therefore rendering the contribution of this compartment to neural coding conditional on the presence of neuromodulators. Long-term regulatory processes, both during development and in the context of activity-dependent plasticity may also affect axonal properties to an underappreciated extent.

Presynaptic But Not Postsynaptic GABA Signaling at Unitary Mossy Fiber Synapses

“…The onset latency of uPSCs from GAD67ϩ GCs was slightly longer than that of uPSCs evoked from GAD67Ϫ GCs, possibly reflecting reduced axonal conduction velocity in these rather immature neurons (Bucher and Goaillard, 2011). Nevertheless, the monosynaptic nature of uPSCs was attested by (1) their short latency (10.7 and 15.6 ms from laser onset, for GAD67Ϫ and GAD67ϩ…”

The Site of Spontaneous Ectopic Spike Initiation Facilitates Signal Integration in a Sensory Neuron

“…There are several examples for such neuromodulator actions in the stomatogastric nervous sys- tem (Meyrand et al, 1992;Combes et al, 1997;Bucher et al, 2003;Goaillard et al, 2004), where eSIZs are activated in the axon trunk. The functional consequences of the elicited ectopic APs are often discussed with reference to their effects on the postsynaptic targets.…”

“…The diameter of the neurites is small compared with the main axon trunk. Morphological inhomogeneities, such as branch points, and rapid changes in axon diameter cause impedance mismatches that affect the current flow and conduction velocity (for review, see Bucher and Goaillard, 2011). Specifically, a decrease in diameter results in reduced capacitance and lower rheobase.…”

“…In the Jonah crab (Cancer borealis), part of the normal activity repertoire of AGR is the generation of spontaneous tonic spike activity in its axon trunk, far away from its sensory dendrites (ectopic spike initiation) (Smarandache and Stein, 2007;Smarandache et al, 2008;Hedrich et al, 2009). Ectopic AP initiation is prevalent in at least some invertebrate and mammalian axons, influencing the neurons' signal processing abilities (Calabrese, 1980;Maranto and Calabrese, 1984;Pinault, 1990;Meyrand et al, 1992;Bostock and Bergmans, 1994;Kiernan et al, 1997;Bucher et al, 2003;Goaillard et al, 2004;Lang et al, 2006;Papatheodoropoulos, 2008;Sheffield et al, 2011). Ectopic spikes can be initiated by application of neuromodulators, such as amines or peptides (for review, see Pinault, 1995;Bucher and Goaillard, 2011), but some neurons spontaneously generate ectopic spike activity in the axon trunk (Maranto and Calabrese, 1984;Pinault, 1990;Daur et al, 2009;Sheffield et al, 2011).…”

Cognitive and behavioral deficits arising from neurodegeneration and traumatic brain injury: a model for the underlying role of focal axonal swellings in neuronal networks with plasticity

“…From a signal processing point of view, recent reviews highlight the fact that axons do more than just faithfully transmit spike train encodings from upstream to downstream neurons: they are responsible for important signal and information processing [47][48][49][50]. Thus when considered in a network architecture, it is not coincidental that FAS, axonal deformation, regional compactation, and myelin abnormalities resulting from TBI in humans [51,52], rodents [53], and swine [54], are directly related to post-traumatic cognitive, physical and psychosocial dysfunctions.…”