Cold-activated raphe-spinal neurons in rats

1. In a search for sympathetic premotor neurons subserving thermoregulatory functions, medullary raphe-spinal neurons were studied in urethane-anaesthetized, artificially ventilated, paralysed rats. Extracellular unit recordings were made from a region previously shown to drive the sympathetic supplies to tail vessels and brown adipose tissue. Neurons that were antidromically activated by stimulation across the intermediate region of the upper lumbar cord (the origin of the tail sympathetic outflow) were selected for study. 2. Non-noxious cooling stimuli were delivered to the animal's shaved trunk by circulating cold instead of warm water through a water jacket. Cooling increased the activity of 21 out of 76 raphe-spinal neurons by 1.0 +/- 0.2 spikes s(-1 degrees)C(-1) for falls in skin temperature of 3-5 degreesC below a threshold of 35.0 +/- 0.6 degreesC. Their responses followed skin temperature in a graded manner, and did so whether or not there was any change in core (rectal) temperature. 3. Indirect observations suggested that seven of the neurons that were activated by skin cooling were also activated by falls in core temperature (by 2.1 +/- 0.7 spikes s(-1) degreesC(-1) below a threshold of 36.1 +/- 0.7 degreesC), while the remainder were unaffected by core cooling. 4. An additional 7/76 raphe-spinal neurons showed evidence of inhibition (activity reduced by 2.1 +/- 0.5 spikes s(-1) degreesC(-1)) when the trunk skin was cooled. 5. Cold-activated raphe-spinal neurons were found in the nuclei raphe magnus and pallidus, centred at the level of the caudal part of the facial nucleus. Their spinal axons conducted at velocities between 3.4 and 29 in s(-1) (median 6.8). 6. Drug-induced rises in arterial pressure partially inhibited the discharge of 6/14 cold-activated raphe-spinal neurons. Weak-to-moderate cardiac modulation (10-70 %) was present in arterial pulse-triggered histograms of the activity of 11/21 cold-activated raphe-spinal neurons, and 6/6 showed evidence of ventilatory modulation (two strongly, four weakly) in pump-triggered histograms. 7. Raphe-spinal neurons responded to cooling in the absence of any change in the electroencephalogram pattern (6/6 neurons). 8. Most cold-activated raphe-spinal neurons responded to noxious tail pinch (13/21 inhibited, 6/21 excited), as did most thermally unresponsive raphe-spinal cells in the same region (19/41 excited, 9/41 inhibited). 9. It is suggested that these cold-activated raphe-spinal neurons may constitute a premotor pathway that drives sympathetically mediated cold defences, such as cutaneous vasoconstriction or thermogenesis. The data are consistent with the hypothesis that a brainstem reflex, with additional descending input signalling body core temperature, may mediate autonomic responses to environmental cooling.