Chen J, Heinke B, Sandkühler J
Institute of Physiology and Pathophysiology, University of Heidelberg, 69120, Heidelberg, Germany.
Neuropharmacology. 2000 Sep;39(12):2231-43. doi: 10.1016/s0028-3908(00)00084-8.
Low-frequency stimulation of primary afferent Adelta-fibers can induce long-term depression of synaptic transmission in rat superficial spinal dorsal horn. Here, we have identified another form of long-term depression in superficial spinal dorsal horn neurons that is induced by specific group I but not group II metabotropic glutamate receptor (mGluR) agonists. Synaptic strength between Adelta-fibers and dorsal horn neurons was examined by intracellular recordings in a spinal cord-dorsal root slice preparation from young rat. In the presence of bicuculline and strychnine, bath application of (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid ((1S,3R)-ACPD) or the specific group I mGluR agonist (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) but not the specific group II mGluR agonist (2S,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl)glycine (DCG-IV) for 20 min produced an acute and a long-term depression of synaptic strength. Bath application of the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovaleric acid did not affect these depressions by (1S,3R)-ACPD. After pre-incubation of slices with pertussis toxin, a G-protein inhibitor, (1S,3R)-ACPD still induced acute and long-term depressions. The phospholipase C inhibitor U73122 stereoselectively blocked the induction of long-term depression without affecting acute synaptic inhibition. This study demonstrates that, in the spinal cord, direct activation of group I mGluRs that are coupled to phospholipase C through pertussis toxin-insensitive G-proteins induces a long-term depression of synaptic strength. This may be relevant to the processing of sensory information in the spinal cord, including nociception.
对初级传入Aδ纤维进行低频刺激可诱导大鼠脊髓背角浅层突触传递的长时程抑制。在此，我们在脊髓背角浅层神经元中发现了另一种形式的长时程抑制，它由特定的I组而非II组代谢型谷氨酸受体（mGluR）激动剂诱导产生。通过在幼鼠脊髓 - 背根切片标本中进行细胞内记录，检测Aδ纤维与背角神经元之间的突触强度。在荷包牡丹碱和士的宁存在的情况下，浴槽应用（1S,3R）-1 - 氨基环戊烷 - 1,3 - 二羧酸（（1S,3R）-ACPD）或特定的I组mGluR激动剂（S）-3,5 - 二羟基苯甘氨酸（（S）-3,5 - DHPG）而非特定的II组mGluR激动剂（2S,2'R,3'R）-2 - （2',3'-二羧基环丙基）甘氨酸（DCG-IV）持续20分钟，可产生突触强度的急性和长时程抑制。浴槽应用N - 甲基 - D - 天冬氨酸受体拮抗剂D - 2 - 氨基 - 5 - 磷酸戊酸不影响（1S,3R）-ACPD引起的这些抑制。在用百日咳毒素（一种G蛋白抑制剂）预孵育切片后，（1S,3R）-ACPD仍能诱导急性和长时程抑制。磷脂酶C抑制剂U73122立体选择性地阻断长时程抑制的诱导，而不影响急性突触抑制。本研究表明，在脊髓中，通过对百日咳毒素不敏感的G蛋白与磷脂酶C偶联的I组mGluR的直接激活可诱导突触强度的长时程抑制。这可能与脊髓中感觉信息的处理有关，包括伤害感受。
