Abstract
Axonal spike initiation at sites far from somatodendritic integration occurs in a range of systems, but its contribution to neuronal output activity is not well understood. We studied the interactions of distal and proximal spike initiation in an unmyelinated motor axon of the stomatogastric nervous system in the lobster, Homarus americanus. The peripheral axons of the pyloric dilator (PD) neurons generate tonic spiking in response to dopamine application. Centrally generated bursting activity and peripheral spike initiation had mutually suppressive effects. The two PD neurons and the electrically coupled oscillatory anterior burster (AB) neuron form the pacemaker ensemble of the pyloric central pattern generator, and antidromic invasion of central compartments by peripherally generated spikes caused spikelets in AB. Antidromic spikes suppressed burst generation in an activity-dependent manner: slower rhythms were diminished or completely disrupted, while fast rhythmic activity remained robust. Suppression of bursting was based on interference with the underlying slow wave oscillations in AB and PD, rather than a direct effect on spike initiation. A simplified multi-compartment circuit model of the pacemaker ensemble replicated this behavior. Antidromic activity disrupted slow wave oscillations by resetting the inward and outward current trajectories in each spike interval. Centrally generated bursting activity in turn suppressed peripheral spike initiation in an activity-dependent manner. Fast bursting eliminated peripheral spike initiation, while slower bursting allowed peripheral spike initiation to continue during the intervals between bursts. The suppression of peripheral spike initiation was associated with a small after-hyperpolarization in the sub-millivolt range. A realistic model of the PD axon replicated this behavior and showed that a sub-millivolt cumulative after-hyperpolarization across bursts was sufficient to eliminate peripheral spike initiation. This effect was based on the dynamic interaction between slow activity-dependent hyperpolarization caused by the Na+/K+-pump and inward rectification through the hyperpolarization-activated inward current, Ih. These results demonstrate that interactions between different spike initiation sites based on spike propagation can shift the relative contributions of different types of activity in an activity-dependent manner. Therefore, distal axonal spike initiation can play an important role in shaping neural output, conditional on the relative level of centrally generated activity.
Highlights
Action potentials are initiated at a single site, usually the soma or proximal axon, as the result of integration of somatodendritic synaptic inputs or endogenous membrane oscillations
Spikes generated during bursts on top of slow wave depolarizations show a longer delay, indicating that they are generated in the STG and propagate the entire length of the nerves to the pdn
The positive delay indicates that the peripheral spike initiation site is closer to the soma than to the pdn, as no delay would indicate equidistance, and negative delay would indicate a more distal initiation site
Summary
Action potentials (spikes) are initiated at a single site, usually the soma or proximal axon, as the result of integration of somatodendritic synaptic inputs or endogenous membrane oscillations. Some neurons exhibit distal axonal spike initiation, not directly resulting from somatodendritic integration (Bucher and Goaillard, 2011; Debanne et al, 2011; Sasaki, 2013; Bucher, 2015; Rama et al, 2018) Such spike initiation is unequivocally “ectopic” when it occurs in abnormal places, which is a common phenomenon in a range of neuropathies associated with injury, demyelination, inflammation, or seizure activity (Stasheff et al, 1993; Pinault, 1995; Poliak and Peles, 2003; Ma and LaMotte, 2007; Krishnan et al, 2009; Connors and Ahmed, 2011; Hamada and Kole, 2015; Meacham et al, 2017). Hippocampal interneurons and pyramidal cells generate such spikes in a range of different network states, which has been proposed to contribute to network oscillations and memory formation (Pinault, 1995; Avoli et al, 1998; Epsztein et al, 2010; Bahner et al, 2011; Connors and Ahmed, 2011; Sheffield et al, 2011; Dugladze et al, 2012; Bukalo et al, 2013; Sheffield et al, 2013; Buzsaki, 2015)
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