title: Burst discharge in primary sensory neurons: triggered by subthreshold oscillations, maintained by depolarizing afterpotentials.
abstract: Afferent discharge generated ectopically in the cell soma of dorsal root ganglion (DRG) neurons may play a role in normal sensation, and it contributes to paraesthesias and pain after nerve trauma. This activity is critically dependent on subthreshold membrane potential oscillations; oscillatory sinusoids that reach threshold trigger low-frequency trains of intermittent spikes. Ectopic firing may also enter a high-frequency bursting mode, however, particularly in the event of neuropathy. Bursting greatly amplifies the overall ectopic barrage. In the present report we show that subthreshold oscillations and burst discharge occur in vivo, as they do in vitro. We then show that although the first spike in each burst is triggered by an oscillatory sinusoid, firing within bursts is maintained by brief regenerative post-spike depolarizing afterpotentials (DAPs). Numerical simulations were used to identify the cellular process underlying rebound DAPs, and hence the mechanism of the spike bursts. Finally, we show that slow ramp and hold (tonic) depolarizations of the sort that occur in DRG neurons during physiologically relevant events are capable of triggering sustained ectopic bursting, but only in cells with subthreshold oscillatory behavior. Oscillations and DAPs are an essential substrate of ectopic burst discharge. Therefore, any consideration of the ways in which cellular regulation of ion channel synthesis and trafficking implement normal sensation and, when disrupted, bring about neuropathic pain must take into account the effects of this regulation on oscillations and bursting.
authors.affiliation: Department of Cell and Animal Biology, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Amir
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Marshall
authors.initials: M
authors.lastname: Devor
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D019771:Axotomy; D001683:Biological Clocks / Q000502:physiology*; D003198:Computer Simulation; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D009475:Neurons, Afferent / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000502:physiology; D012684:Sensory Thresholds / Q000502:physiology
chemical_list: D004837:Epinephrine