The planned experiments explore the role of presynaptic ionotropic glutamate receptors in modulation of sensory input from peripheral nerves. This proposal aims, in the first place, at determining the distribution of presynaptic AMPA, kainate, and NMDA subunits in the dorsal horn of the spinal cord and in the dorsal column nuclei. I will also determine in what terminals are ionotropic receptors expressed presynaptically, i.e. in primary afferent terminals or also in terminals of interneurons, and if they might play a role in nociception and in presynaptic inhibition. I will determine the type/s of primary afferent terminal and of intrinsic terminals that express different subunits of presynaptic ionotropic glutamate receptors on the basis of morphology, neuroanatomical tracers, and co-expression of other markers suggestive of their functional properties. Finally, I will test the response of presynaptic ionotropic glutamate receptors to peripheral injury and inflammation. The work is based on a light and electron microscopic strategy that involves double- and multiple staining. We have introduced technical modifications, e.g. diluted fixation, without which the present proposal would not have been possible. Besides providing an essentially descriptive overview of the expression and distribution of subunits of the AMPA, kainate and NMDA, we will answer specific questions addressing the possible functional role of presynaptic receptors. These questions and the strategies to answer them are now specifically listed throughout the text and summarized in the conclusions of this revised proposal.
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