We plan to continue using intracellular recordings in the isolated (in vitro) spinal cord preparation of the frog to examine the role of serotonin (5-hydroxytryptamine, 5-HT) in the descending control of spinal dorsal horn neurons. We have made considerable progress in describing (for the first time) the effects of 5-HT on the membrane potential and input resistance of dorsal horn neurons. We have also determined the types of 5-HT receptors mediating these responses, and obtained an indication of the ionic mechanisms associated with each receptor type. In the present proposal, we would like to further examine the neuronal circuitry and mechanism(s) of 5-HT action in the dorsal horn by addressing issues related to:' (1) the presence, or lack thereof, of an enkephalin (ENK) or gamma-aminobutyric acid (GABA) link in serotonin's inhibitory action in the dorsal horn, (2) the manner in which 5-HT modifies excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of different types of primary afferent fibers (i.e., how might 5-HT indirectly inhibit the nociceptive input to the dorsal horn?), (3) the presence, or lack thereof, of a novel 5-HT receptor in the frog dorsal horn, and (4) the implication for sensory processing of our observation that some dorsal horn neurons appear to selectively process (filter) dorsal root-evoked subthreshold EPSPs arriving at different times - does 5-HT increase or decrease the filter bandwidth? This proposal should increase our knowledge of nociception at medullary and spinal levels, and this knowledge might lead to significant advances in dental and cutaneous pain management.
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