Real time imaging of neuronal excitation and cellular morphology of plastic synapses

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It is now believed that the long-term depression of synaptic transmissions from primary afferent C fibers to spinal dorsal horn neurons after conditioning low-frequency stimulation of A fibers take a critical role in the analgesia by adequate electrical or tactile stimulation. It is also known that dendritic morphology of some dorsal horn neurons is altered after the application of substance P, the pain transmitter/modulator released from pain-conducting primary afferent fibers. Therefore, it has been speculated that the morphological change might be caused by hyperalgesia and/or allodynia, and that it might be reset by analgesics such as morphine. The purpose of the present research is thus to reveal the properties of neuronal plasticity in the spinal dorsal horn. Especially, plastic changes in the neuronal excitation and neuronal morphology in the substantia gelatinosa of the dorsal horn are to be studied by using optical imaging methods with voltage sensitive dyes and con-focal micr … More oscope.We have revealed that conditioning high-frequency stimulation of A fibers in the dorsal root robustly changed C-fiber-evoked neuronal excitation, a facilitation under a low activity of inhibitory interneurons containing inhibitory amino acids, and suppression at the high activity. Conditioning low-frequency stimulation inhibited the induction and maintenance of the high-frequency conditioning-induced facilitation. Dendritic varicosities of some dorsal horn neurons in the gelatinosa, stained with DiI by the micro oil-drop method and observed with a laser-scan con-focal microscope, were expanded after the application of conditioning.These results thus exhibited clearly by optical imaging techniques, plastic changes in the dorsal horn, both in the signal transmission and in the neuronal morphology, take place by the conditioning stimulations known to induce hyperalgesia, allodynia or analgesia, and strongly indicated that such plasticity might be essential for the induction and transmission of the pain. Less