Resetting of sympathetic rhythm by somatic afferents causes post-reflex coordination of sympathetic activity in rat

Abstract

1. We have proposed previously that graded synchronous activity is produced by periodic inputs acting on weakly coupled or uncoupled oscillators influencing the discharges of a population of cutaneous vasoconstrictor sympathetic postganglionic neurones (PGNs) in anaesthetized rats. 2. Here we investigated the effects of somatic afferent (superficial radial nerve, RaN) stimulation, on the rhythmic discharges of this population. We recorded (1) at the population level from the ventral collector nerve and (2) from single PGNs focally from the caudal ventral artery of the tail. 3. Following RaN stimulation we observed an excitatory response followed by a period of reduced discharge and subsequent rhythmical discharges seemingly phase-locked to the stimulus. 4. We suggest that the rhythmical discharges following the initial excitatory response (conventional reflex) result from a resetting of sympathetic rhythm generators such that rhythmic PGN activity is synchronized transiently. We also demonstrate that a natural mechanical stimulus can produce a similar pattern of response. 5. Our results support the idea that in sympathetic control, resetting of multiple oscillators driving the rhythmic discharges of a population of PGNs may provide a mechanism for producing a sustained and coordinated response to somatic input.

Figure 1. Response of VCN to RaN stimulation and sham stimulation in the absence of CRD

A, RaN stimulation. B, sham stimulation. Aa and Ba, autospectra of VCN activity. Under the two conditions there is a similar broad peak (0.73 Hz) in the relative power density (RPD). Ab and Bb, stimulus-triggered waveform-averaged responses (42 triggers) of smoothed and rectified VCN activity. The filled circle indicates an artefact of the stimulation. ‘1’ indicates the short-latency component of the response. ‘2′ and ‘3′ are burst discharges. Ac and Bc, stimulus-triggered waveform-averaged responses of smoothed and rectified PN activity. Neither RaN stimulation (Ac) nor sham stimulation (Bc) has a significant influence on CRD. For comparison, the averaged waveform of full-inspiratory-related bursts is shown in the middle panel. C, three sample sweeps of smoothed and rectified VCN activity triggered by RaN stimulation.

Figure 2. Discharge response of a single PGN to RaN stimulation

A and B, RaN stimulation and sham stimulation, respectively, under normal CRD conditions. Aa and Ba, autocorrelograms reveal the same dominant rhythm under RaN and sham stimulation conditions (0.68 Hz). Ab and Bb, stimulus-PGN cross-correlograms (85 triggers). RaN stimulation evokes an initial discharge followed by a period of reduced firing and then rhythmical bursting. Inset in Ab is the sham stimulation autocorrelogram (Ba) on the same timebase. Ac and Bc, stimulus-PN cross-correlograms show no stimulus-related activity. Ad and Bd, stimulus-triggered (tr) raster plots for RaN stimulation (Ad) reveal clear vertical striations (arrowheads) indicating a consistent temporal response pattern compared to sham stimulation (Bd). Ae and Be, PGN raster plots reordered by the first post-stimulus interevent interval for each stimulation (see Chang et al. 2000). Ae, vertical bands (vertical arrowheads) indicate a constant phase relationship with respect to RaN stimulation. The pre-stimulation diagonal band (diagonal arrowhead) reveals a variable phase relationship with the stimulus. Be, under sham stimulation conditions only diagonal bands (diagonal arrowheads) are seen. Ca, two sample neurograms showing the response of a single PGN to RaN stimulation. Cb, 10 overlapping sweeps of PGN spikes from the unit in Ca.

Figure 3. Simultaneous recording of two PGNs during RaN stimulation and sham stimulation

Aa and b, stimulus-PGN1 and stimulus-PGN2 cross-correlograms show the same characteristic pattern of response seen in Fig. 2. The insets show autocorrelograms of the dominant rhythms of PGN1 (0.59 Hz) and PGN2 (0.73 Hz). Ba and b, sham stimulus-PGN1 and sham stimulus-PGN2 cross-correlograms show no evidence of patterned activity in relation to sham stimulation events. C and D, joint peri-stimulus scatter plot showing the joint firing probability of the two PGNs in relation to the RaN stimulus (C) and the sham stimulus (D). C, RaN stimulation leads to coincident rhythmical bursting, illustrated by dense patches (arrows), which become less defined as time from the stimulus increases. D, sham stimulation does not lead to periodic patterned activity. In both C and D, weak non-periodic coincident activity clusters along the 45 deg diagonal line (arrowheads); a phenomenon reflecting inconsistent, near-zero lag synchronization, which has been described previously (Chang et al. 1999). RaN st, RaN stimultion; sh st, sham stimulation.

Figure 4. Summary of the characteristics of RaN stimulation-evoked single PGN activity

A, scatter plot showing the relationship between the dominant rhythm period for each PGN recorded and the latency of the three main RaN-evoked burst discharges (‘a’, ‘b’ and ‘c’; see schematic diagram, inset). ‘a’ and ‘b’ are not significantly correlated with the dominant rhythm period while ‘c’ is significantly positively correlated. B, scatter plot of the dominant rhythm frequency (Hz) for each PGN against the post-RaN stimulus rhythm (calculated as 1/(c - b)). The dominant rhythm and the post-stimulus rhythm are significantly positively correlated. The histogram in the inset shows the median ± IQR frequency for the dominant rhythm (d) and the post-stimulus rhythm (p-s). The median frequencies of the dominant and post-stimulus rhythm are not significantly different. C, scatter plot of discharge rate (Hz) of each single PGN during RaN stimulation vs. sham stimulation. The discharge rates under these conditions are significantly positively correlated. The histogram in the inset shows the median ± IQR discharge rate under RaN stimulation (st) and sham stimulation (sh) conditions. The median discharge rates are not significantly different. For B and C, PGNs recorded in both the absence of CRD (♦) and normal CRD (⋄) are shown. See Results for more details.

Figure 5. Response of single PGN discharges to a pinch of the forepaw in the absence of CRD

A, mechanical stimulation. B, sham stimulation. Aa and Ba, autocorrelograms showing that the dominant rhythm under the two conditions was the same (0.68 Hz). Ab and Bb, stimulus-PGN cross-correlogram (18 triggers) under both conditions. The inset in Ab is the sham stimulation autocorrelogram (Ba). Ac and Bc, stimulus triggered (tr)-PGN raster plots under both conditions. In response to forepaw pinch (Ac) clear vertical striations can be observed (arrowheads) illustrating the consistency of the response across time.