| The Ca2+-permeable subtype of AMPA receptors has been shown to mediate both short and long-term changes in synaptic strength. In this study, we have examined the localization of functional Ca2+-permeable AMPA receptors in the spinal cord dorsal horn, the area where nociceptive primary afferents first relay information to the central nervous system at fast glutamatergic synapses. Using pharmacology and immunolocalization of AMPA receptor subunits, we have demonstrated that kainate-induced cobalt staining is a functional marker of neurons expressing Ca2+-permeable AMPA receptors. We have shown that cobalt-positive neurons are located in lamina I and outer lamina II of the dorsal horn, a region strongly innervated by nociceptors. We have also found that some NK1-positive putative projection neurons express functional Ca2+-permeable AMPA receptors.; Based on the enrichment of Ca2+-permeable AMPA receptors in inhibitory interneurons throughout the nervous system, and suggestions that these receptors may presynaptically modulate GABA release, we have also tested for a presynaptic role of Ca2+-permeable AMPA receptors in dorsal horn inhibitory interneurons. In recordings from dorsal horn neurons in spinal cord slices, we used a selective AMPA receptor agonist and antagonist to demonstrate that AMPA receptors can modulate inhibitory amino acid release from presynaptic sites. We have shown that this change in release is sensitive to the concentration of extracellular Ca2+, yet is not fully blocked in most neurons in the presence of Cd2+, suggesting that voltage activated Ca2+ channels are not necessary for the effect, and that the Ca2+-permeable subtype of AMPA receptor may mediate this presynaptic modulation. We have also shown that AMPA-induced increases in mIPSC frequency can be seen in more mature dorsal horn, suggesting that these receptors may play a role in nociceptive processing in the adult.; The presence of Ca2+-permeable AMPA receptors in both dorsal horn projection neurons and inhibitory interneurons suggests that these receptors may have complex roles in nociceptive neurotransmission. |
