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J Comput Neurosci. 2015 Aug;39(1):17-28. doi: 10.1007/s10827-015-0562-8. Epub 2015 May 1.

Cooperativity between remote sites of ectopic spiking allows afterdischarge to be initiated and maintained at different locations.

Author information

1
NeuroLinx Research Institute, PO Box 13668, La Jolla, CA, 92039, USA, jay@neurolinx.org.

Abstract

Many symptoms of nerve damage arise from ectopic spiking caused by hyperexcitability. Ectopic spiking can originate at the site of axonal damage and elsewhere within affected neurons. This raises the question of whether localized damage elicits cell-wide changes in excitability and/or if localized changes in excitability can drive abnormal spiking at remote locations. Computer modeling revealed an example of the latter involving afterdischarge (AD)--stimulus-evoked spiking that outlasts stimulation. We found that AD originating in a hyperexcitable region of axon could shift to the soma where it was maintained. This repositioning of ectopic spike initiation was independent of distance between the two sites but relied on the rate and number of ectopic spikes originating from the first site. Nonlinear dynamical analysis of a reduced model demonstrated that properties which rendered the axonal site prone to initiating AD discouraged it from maintaining AD, whereas the soma had the inverse properties thus enabling the two sites to interact cooperatively. A first phase of AD originating in the axon could, by providing sufficient drive to trigger somatic AD, give way to a second phase of AD originating in the soma such that spiking continued when axonal AD failed. Ectopic spikes originating from the soma during phase 2 AD propagated successfully through the defunct site of axonal spike initiation. This novel mechanism whereby ectopic spiking at one site facilitates ectopic spiking at another site is likely to contribute to the chronification of hyperexcitability in conditions such as neuropathic pain.

PMID:
25929191
PMCID:
PMC4496271
DOI:
10.1007/s10827-015-0562-8
[Indexed for MEDLINE]
Free PMC Article

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