Silent synapses and long-term potentiation in the spinal cord analyzed by imaging of pre- and postsynaptic excitation

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Pain-conducting primary afferent fibers terminate in superficial parts of the spinal dorsal horn. The afferent synapses are plastic and long-term potentiation of the synaptic efficacy is considered to be responsible for the induction of the Hyperalgesia at least in part. We have investigated the plasticity by imaging neuronal excitation in spinal cord slices stained with voltage dye. Recently we succeeded to image more specifically the excitation of pre and postsynaptic elements, namely (1) retrograde staining of afferent fibers to visualize presynaptic events, and (2) anterograde staining of projection neurons in the superficial dorsal horn to visualize postsynaptic events. In preliminary experiments, we observed two interesting events. One is that after conditioning stimulation, silent synapses became active and also silent afferent terminals started generating action potentials. Another is that nitric oxide (NO) contributed to the induction.In this study, we first investigated on th … More e mechanism how the silent synapses become active by using the retrograde and anterograde staining of pre and postsynaptic elements, respectively. We have confirmed that after conditioning, presynaptic terminals started generating action potentials and thus silent synapses became active. Secondly, we tried to reveal the signaling pathway through which NO induced the potentiation by using double staining of slice with voltage dye and NO-sensitive dye. We have shown that the amount of NO released after conditioning is strongly correlated with the degree of long-term potentiation. In addition, we have shown that, after the treatment with a glial metabolism inhibitor, both induction of long-term potentiation and NO release did not take place, results suggesting glial cells contribute for the NO release. Thirdly, we investigated the mechanism how glial cells contribute to the long-term potentiation, especially whether or not ATP contribute to it. We have obtained results showing that neuron-glia interactions via P2X receptors of ATP is essential for the induction of long-term potentiation. Fourthly, we have revealed the mechanism of presynaptic inhibition via presynaptic vanilloid receptors that is ATP- and temperature dependent. Less