Cells in laminae III and IV of the rat spinal cord which possess the neurokinin‐1 receptor receive monosynaptic input from myelinated primary afferents

Abstract

We have previously demonstrated that neurons which have cell bodies in laminae III or IV of the rat spinal cord, dendrites that enter the superficial laminae and which possess the neurokinin-1 receptor receive a major synaptic input from substance P-containing primary afferent axons. In this study we set out to determine whether these cells also receive monosynaptic input from myelinated primary afferents by using transganglionic transport of the B subunit of cholera toxin to identify the central terminals of myelinated afferents from the sciatic nerve. Dual-immunofluorescence and confocal microscopy revealed apparent contacts between labelled primary afferent terminals and all of the neurokinin-1 receptor-immunoreactive cells examined, although these contacts were much less numerous than those which the cells receive from substance P-containing primary afferents. By using a combined confocal and electron microscopic technique we were able to confirm that synapses were present at some of the contacts between primary afferents and neurokinin-1 receptor-immunoreactive neurons. These results suggest that cells of this type will have wide-dynamic range receptive fields, but with a relatively strong input from nociceptors.

GABAergic Neurons that Contain Neuropeptide Y Selectively Target Cells with the Neurokinin 1 Receptor in Laminae III and IV of the Rat Spinal Cord

“…1 A). As described previously, these cells also often had dendrites that remained in the deeper laminae (Brown et al, 1995;Naim et al, 1997Naim et al, , 1998. The distribution of N PY immunoreactivity was also the same as that reported in previous studies in the rat (Hökfelt et al, 1981;Hunt et al, 1981;Sasek and Elde, 1985;Rowan et al, 1993): a dense plexus of N PY-immunoreactive axons was observed in laminae I and II ( Fig.…”

“…Sections were examined with a Bio-Rad (Hemel Hempstead, UK) MRC 1024 confocal scanning laser microscope with a Krypton-Argon laser (Naim et al, 1997(Naim et al, , 1998. N K1 receptor-immunoreactive neurons with cell bodies located Ͼ150 m below the dorsal white matter (in lamina III or IV) and dendrites that could be traced into lamina II were selected for f urther study.…”

“…Sequential scans obtained with a 40ϫ oil-immersion lens were then used to reveal the positions of contacts from N PYimmunoreactive varicosities onto their cell bodies and dendrites, and these were recorded and plotted onto the drawings. The frequency of N PY contacts per unit length of dendrite for each of these cells was determined by measuring the length of each dendrite from z-series with Neurolucida for Confocal (MicroBrightField Inc., Colchester, V T) as described previously (Naim et al, 1998). Because the density of N PY boutons is higher in the superficial dorsal horn than in deeper laminae, we determined the density of contacts separately for those dendrites that lay within laminae I and II and for dendrites in deeper laminae.…”

“…The majority of N PY boutons that were apposed to the neurons formed synapses, and these are likely to mediate the parallel GABAergic inhibitory role of the NPY-containing axons. Because lamina III / IV N K1 receptorimmunoreactive neurons also receive some input from myelinated primary afferents, which are likely to be low-threshold mechanoreceptors (Naim et al, 1998), the N PY-containing inhibitory interneurons may also regulate the flow of information conveyed by these afferents.…”

Disinhibition Opens the Gate to Pathological Pain Signaling in Superficial Neurokinin 1 Receptor-Expressing Neurons in Rat Spinal Cord

“…Morphologically, they receive limited myelinated afferent input as well as dense innervation from substance P-containing primary afferents in lamina I/II. They have been likened to wide dynamic range neurons (Naim et al, 1997(Naim et al, , 1998) and project to the brainstem (Todd et al, 2000) and thalamus (Marshall et al, 1996). The other subgroup of lamina III/IV, NK1Rϩ neurons have more restricted dendritic trees.…”