Abstract
The spinal dorsal horn contains numerous inhibitory interneurons that control transmission of somatosensory information. Although these cells have important roles in modulating pain, we still have limited information about how they are incorporated into neuronal circuits, and this is partly due to difficulty in assigning them to functional populations. Around 15% of inhibitory interneurons in laminae I-III express neuropeptide Y (NPY), but little is known about this population. We therefore used a combined electrophysiological/morphological approach to investigate these cells in mice that express green fluorescent protein (GFP) under control of the NPY promoter. We show that GFP is largely restricted to NPY-immunoreactive cells, although it is only expressed by a third of those in lamina I-II. Reconstructions of recorded neurons revealed that they were morphologically heterogeneous, but never islet cells. Many NPY-GFP cells (including cells in lamina III) appeared to be innervated by C fibres that lack transient receptor potential vanilloid-1, and consistent with this, we found that some lamina III NPY-immunoreactive cells were activated by mechanical noxious stimuli. Projection neurons in lamina III are densely innervated by NPY-containing axons. Our results suggest that this input originates from a small subset of NPY-expressing interneurons, with the projection cells representing only a minority of their output. Taken together with results of previous studies, our findings indicate that somatodendritic morphology is of limited value in classifying functional populations among inhibitory interneurons in the dorsal horn. Because many NPY-expressing cells respond to noxious stimuli, these are likely to have a role in attenuating pain and limiting its spread.
Highlights
Inhibitory interneurons, which account for ;30% of the neurons in laminae I-III of the spinal dorsal horn,[44] are important in controlling the transmission of sensory inputs perceived as pain or itch[2,11,12,31,51,61] and represent potential targets for treatments designed to relieve these symptoms
GFP1 cells were present throughout the dorsal horn, their density was relatively low in laminae I-II, while they were more numerous in lamina III (Fig 1A)
The main findings of this study are (1) that neuropeptide Y (NPY)-green fluorescent protein (GFP) cells are morphologically diverse and that those in lamina II do not consistently fit into any of the morphological classes identified in this lamina,[15] (2) that they include a specific subset with axons that contribute to the dense bundles of NPY axons that are associated with projection neurons in lamina III, and (3) that most of them were not innervated by transient receptor potential vanilloid-1 (TRPV1)-expressing primary afferents
Summary
Inhibitory interneurons, which account for ;30% of the neurons in laminae I-III of the spinal dorsal horn,[44] are important in controlling the transmission of sensory inputs perceived as pain or itch[2,11,12,31,51,61] and represent potential targets for treatments designed to relieve these symptoms. We still know relatively little about their organisation or about the synaptic circuits through which they modulate sensory transmission. This is largely due to the difficulty in identifying distinct populations among these cells.[14,61] A widely used morphological classification scheme for lamina II interneurons defines 4 major. Most studies of lamina II neurons have found that ;25% of these cells could not be classified morphologically,[15,19,76] and little is known about the relation between morphology and function for interneurons in laminae I and III.[49,54]
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