@article {LarssonENEURO.0007-19.2019, author = {Max Larsson and Jonas Broman}, title = {Synaptic organization of VGLUT3 expressing low-threshold mechanosensitive C fiber terminals in the rodent spinal cord}, elocation-id = {ENEURO.0007-19.2019}, year = {2019}, doi = {10.1523/ENEURO.0007-19.2019}, publisher = {Society for Neuroscience}, abstract = {Low-threshold mechanosensitive C fibers (C-LTMRs) that express the vesicular glutamate transporter VGLUT3 are thought to signal affective touch, and may also play a role in mechanical allodynia. However, the nature of the central termination of C-LTMRs in the dorsal horn remains largely unexplored. Here we used light and electron microscopy in combination with VGLUT3 immunolabeling as a marker of C-LTMR terminations to investigate this issue. VGLUT3+ C-LTMRs formed central terminals of type II glomeruli in the inner part of lamina II of the dorsal horn, often establishing multiple asymmetric synapses with postsynaptic dendrites but also participating in synaptic configurations with presynaptic axons and dendrites. Unexpectedly, essentially all VGLUT3+ C-LTMR terminals showed substantial VGLUT1 expression in the rat, whereas such terminals in mice lacked VGLUT1. Most VGLUT3+ C-LTMR terminals exhibited weak-to-moderate VGLUT2 expression. Further, C-LTMR terminals formed numerous synapses with excitatory protein kinase Cγ interneurons and inhibitory parvalbumin neurons, whereas synapses with calretinin neurons were scarce. C-LTMR terminals rarely if ever established synapses with neurokinin 1 receptor-possessing dendrites traversing lamina II. Thus, VGLUT3+ C-LTMR terminals appear to largely correspond to neurofilament-lacking central terminals of type II glomeruli in inner lamina II and can thus be identified at the ultrastructural level by morphological criteria. The participation of C-LTMR terminals in type II glomeruli involving diverse populations of interneuron indicates highly complex modes of integration of C-LTMR mediated signaling in the dorsal horn. Furthermore, differences in VGLUT1 expression indicate distinct species differences in synaptic physiology of C-LTMR terminals.Significance Statement Here we show that low-threshold mechanosensitive C fibers (C-LTMRs) form central terminals of a certain class of synaptic glomeruli, where they are subject to presynaptic inhibition and establish synapses onto distinct populations of excitatory and inhibitory interneurons in the dorsal horn. These results prompt a revised interpretation of dorsal horn ultrastructure, and provide a basis for ultrastructural identification of C-LTMRs in future studies of the role of these fibers in somatosensation. Furthermore, our observations indicate that C-LTMR terminations are subject to complex regulation and are well-positioned to participate in integration of afferent signals that lead to percepts of affective touch and pain.}, URL = {https://www.eneuro.org/content/early/2019/02/01/ENEURO.0007-19.2019}, eprint = {https://www.eneuro.org/content/early/2019/02/01/ENEURO.0007-19.2019.full.pdf}, journal = {eNeuro} }