Oscillatory Membrane Potential Activity in the Soma of a Primary Afferent Neuron

146

109

Ectopic discharge generated in injured afferent axons and cell somata in vivo contributes significantly to chronic neuropathic dysesthesia and pain after nerve trauma. Progress has been made toward understanding the processes responsible for this discharge using a preparation consisting of whole excised dorsal root ganglia (DRGs) with the cut nerve attached. In the in vitro preparation, however, spike activity originates in the DRG cell soma but rarely in the axon. We have now overcome this impediment to understanding the overall electrogenic processes in soma and axon, including the resulting discharge patterns, by modifying the bath medium in which recordings are made. At both sites, bursts can be triggered by subthreshold oscillations, a phasic stimulus, or spikes arising elsewhere in the neuron. In the soma, once triggered, bursts are maintained by depolarizing afterpotentials, whereas in the axon, an additional process also plays a role, delayed depolarizing potentials. This alternative process appears to be involved in "clock-like" bursting, a discharge pattern much more common in axons than somata. Ectopic spikes arise alternatively in the soma, the injured axon end (neuroma), and the region of the axonal T-junction. Discharge sequences, and even individual multiplet bursts, may be a mosaic of action potentials that originate at these alternative electrogenic sites within the neuron. Correspondingly, discharge generated at these alternative sites may interact, explaining the sometimes-complex firing patterns observed in vivo.

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multiple Interacting Sites of Ectopic Spike Electrogenesis in Primary Sensory Neurons

Amir¹,

Kocsis²,

Devor³

2005

146

109

“…For type I SA with a bursting or irregular pattern, it was proposed that an oscillation triggered the first spike of each burst of discharges (Amir et al, 1999(Amir et al, , 2002b. The mechanism for SMPO might be attributable to the interaction between a tetrodotoxin (TTX)-sensitive Na ϩ conductance and a passive voltage-independent K ϩ conductance (Pedroarena et al, 1999;Amir et al, 2002a;Enomoto et al, 2006). However, it is not clear which currents might contribute to the different patterns of SA, or to the oscillation-induced triggering of action potentials.…”

Section: Functional Significance Of Spontaneous Ectopic Generators Inmentioning

confidence: 99%

Multiple Sites for Generation of Ectopic Spontaneous Activity in Neurons of the Chronically Compressed Dorsal Root Ganglion

Ma¹,

LaMotte²

2007

108

In a chronically compressed dorsal root ganglion (CCD) in the rat, a model of foraminal stenosis and radicular pain in human, a subpopulation of neurons with functional axons exhibits spontaneous activity (SA) that originates within the ganglion. Intracellular electrophysiological recordings were obtained from the somata of neurons of the compressed ganglion both in vitro and in vivo. The SA was classified into two types according to the presence (type I) or absence (type II) of subthreshold membrane potential oscillation. Neurons with type I SA had significantly higher somal excitability than those with type II SA. In most cases, depolarization of the membrane potential by current injection increased the discharge rates of type I -but not type II SA. Both types occasionally coexisted in the same neuron. Several lines of evidence suggested that the origin of SA in the DRG was most likely the soma for type I SA and the axon for type II. Therefore CCD neurons have multiple sites for generation of action potentials other than the terminal endings. In vivo recordings revealed the same two types of SA in a subpopulation of neurons with functionally characterized peripheral receptive fields. Thus, SA might not only produce spurious sensory input to the afferent pathways but also add to or block impulse transmission generated by natural stimulation of peripheral receptors. SA originating in the compressed ganglion is likely to interfere with sensory transmission in nociceptive and non-nociceptive neurons, thereby contributing to radicular pain, paresthesias, hyperalgesia and allodynia.

“…Recently, it was demonstrated that Mes V neurons show conditional burst generation in response to maintained membrane depolarization (Pedroarena et al, 1999;Wu et al, 2001Wu et al, , 2005. Evidence was provided that I NaP amplifies a K ϩ -dependent membrane resonance to initiate subthreshold membrane oscillations.…”

Section: Introductionmentioning

confidence: 99%

Participation of Sodium Currents in Burst Generation and Control of Membrane Excitability in Mesencephalic Trigeminal Neurons

Enomoto¹,

Han²,

Hsiao³

et al. 2006

Subthreshold sodium currents are important in sculpting neuronal discharge and have been implicated in production and/or maintenance of subthreshold membrane oscillations and burst generation in mesencephalic trigeminal neurons (Mes V). Moreover, recent data suggest that, in some CNS neurons, resurgent sodium currents contribute to production of high-frequency burst discharge. In the present study, we sought to determine more directly the participation of these currents during Mes V electrogenesis using the action potentialclamp method. In postnatal day 8 -14 rats, the whole-cell patch-clamp method was used to record sodium currents by subtraction in response to application of TTX in voltage-clamp mode using the action potential waveform as the command protocol. We found that TTX-sensitive sodium current is the main inward current flowing during the interspike interval, compared with the h-current (I h ) and calcium currents. Furthermore, in addition to the transient sodium current that flows during the upstroke of action potential, we show that resurgent sodium current flows at the peak of afterhyperpolarization and persistent sodium current flows in the middle of the interspike interval to drive high-frequency firing. Additionally, transient, resurgent, and persistent sodium current components showed voltage-and time-dependent slow inactivation, suggesting that slow inactivation of these currents can contribute to burst termination. The data suggest an important role for these components of the sodium current in Mes V neuron electrogenesis.