TY - JOUR
T1 - Burst discharge in primary sensory neurons
T2 - Triggered by subthreshold oscillations, maintained by depolarizing afterpotentials
AU - Amir, Ron
AU - Michaelis, Martin
AU - Devor, Marshall
PY - 2002/2/1
Y1 - 2002/2/1
N2 - 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.
AB - 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.
KW - Depolarizing afterpotential
KW - Dorsal root ganglion
KW - Ectopic firing
KW - Neuropathic pain
KW - Pain
KW - Paresthesia
KW - Subthreshold oscillations
UR - http://www.scopus.com/inward/record.url?scp=0036470142&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.22-03-01187.2002
DO - 10.1523/jneurosci.22-03-01187.2002
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C2 - 11826148
AN - SCOPUS:0036470142
SN - 0270-6474
VL - 22
SP - 1187
EP - 1198
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 3
ER -