Electrical excitability of the soma of sensory neurons is required for spike invasion of the soma, but not for through-conduction

Abstract

The cell soma of primary sensory neurons is electrically excitable, and is invaded by action potentials as they pass from the peripheral nerve, past the dorsal root ganglion (DRG) and toward the spinal cord. However, there are virtually no synapses in the DRG, and no signal processing is known to occur there. Why, then, are DRG cell somata excitable? We have constructed and validated an explicit model of the primary sensory neuron and used it to explore the role of electrical excitability of the cell soma in afferent signaling. Reduction and even elimination of soma excitability proved to have no detectable effect on the reliability of spike conduction past the DRG and into the spinal cord. Through-conduction is affected, however, by major changes in neuronal geometry in the region of the t-junction. In contrast to through-conduction, excitability of the soma and initial segment is essential for the invasion of afferent spikes into the cell soma. This implies that soma invasion has a previously unrecognized role in the physiology of afferent neurons, perhaps in the realm of metabolic coupling of the biosynthesis of signaling molecules required at the axon ends to functional demand, or in cell-cell interaction within sensory ganglia. Spike invasion of the soma in central nervous system neurons may play similar roles.

FIGURE 1

Schematic diagram of our cell model. Normal internodes are indicated in black. Internodes close to the t-junction, that had tapering axon diameter and other abnormalities, are crosshatched (for details, see Methods). The first internode on the stem axon is barely visible due to its thin myelin sheath (Table 1). Note that axonal length and diameter are drawn using different calibrations scales. The soma is round.

FIGURE 2

Soma-spike components. A stimulus pulse delivered to the 20th peripheral node (5 nA, 0.2 ms) evoked a full S-spike in the soma. Reducing pNa_max⁺ in the soma and initial segment from 8 × 10⁻⁵ to 4 × 10⁻⁵ cm/s led to failure of spike invasion, leaving only an NM-spike residue. Note the inflection on the rising phase of the S-spike (arrow) which illustrates the NM component of the S-spike.

FIGURE 3

Changing pNa_max⁺ in the soma and initial segment does not affect spike propagation past the t-junction. A stimulus pulse pair was applied to the 20th peripheral node (first pulse marked with an arrow; IPI, 2.26 ms). Recordings were at R1, R2, and R5 (see Fig. 1). pNa_max⁺ was 40 × 10⁻⁵ cm/s (A, “high”) or 0 cm/s (B). The hump on the falling phase of the second spike recorded at R2 (arrowhead in A) results from the associated soma spike, which was delayed in the case of the second stimulus pulse (also see Fig. 4). In B no soma spike was evoked by either stimulus pulse, and therefore no hump occurred.

FIGURE 4

Changing pNa_max⁺ in the soma and initial segment dramatically affects spike invasion into the soma. A stimulus pulse pair was applied to the 20th peripheral node (IPI, 2.26 ms) and recordings were made near the t-junction (R2 and R3 in Fig. 1) and in the soma (R4 in Fig. 1). The first stimulus pulse is marked with an arrow in bottom trace. The ability of the spike to invade the soma (R4) is compromised as pNa_max⁺ is reduced. At intermediate values of pNa_max⁺ the first spike invaded the soma, but the second spike failed to invade. At lower values, even the first spike failed to invade. Arrowheads in traces R2 and R3 indicate a decremental signal, originating in the soma spike, that is still visible at these recording points near the t-junction. This signal is subthreshold for spike propagation, however, and was not recorded at R1 or R5 (Fig.1, data not shown). Note that using other parameters, the soma spike can generate a back-propagating “extra spike” as shown in Fig. 6. pNa_max⁺ values are: low, 4 × 10⁻⁵ cm/s; medium, 8 × 10⁻⁵ cm/s; high, 24 × 10⁻⁵ cm/s.

FIGURE 5

The effect of pNa_max⁺ in the soma and initial segment on the absolute refractory period (ARP, A) and the corresponding least conduction interval (LCI, B) recorded in the soma (R4), peripheral axon branch (R1), central axon branch (R2) and the t-stem axon (R3). A stimulus pulse pair was applied to the 20th peripheral node. A), Except in the cell soma, ARP remained identical over the entire range of pNa_max⁺ values. When pNa_max⁺ was ≥22 × 10⁻⁵ cm/s ARP for the soma took this same value. The arrow indicates a discontinuity in the soma's ARP function (see Results). For pNa_max⁺ ≤4.5 × 10⁻⁵ cm/s spikes failed to invade the soma (dashed line). B), As expected, the LCI followed the same general pattern as the ARP as pNa_max⁺ was varied, but for soma spikes some values of LCI were chaotic. The physiological value of pNa_max⁺ is ∼8 × 10⁻⁵ cm/s.

FIGURE 6

Events underlying the discontinuity (arrow and crosshatched zone in Fig. 5), in the ARP for spike invasion of the soma. Two stimulus pulses were applied to the peripheral axon (see Fig. 1) and recordings were made from R1 and R4 (Fig. 1). Arrows indicate the time of the first stimulus pulse. Propagation velocity along the axon (R1), and the success of spike invasion into the soma (R4) depended on both pNa_max⁺ and the IPI. Arrowheads in upper panel indicate “extra spikes” evoked by reflection (back-propagation) of the soma spike into the peripheral axon (Tagini and Camino, 1973). An extra spike also entered the central axon.