Lynch M A, Errington M L, Bliss T V
Division of Neurophysiology and Neuropharmacology, National Institute for Medical Research, London, U.K.
Neuroscience. 1989;30(3):693-701. doi: 10.1016/0306-4522(89)90162-0.
The dentate gyrus of anaesthetized rats was perfused with artificial cerebrospinal fluid while field responses evoked by stimulation of the perforant path were monitored. Perfusates were collected for analysis of endogenous glutamate, aspartate and arachidonate. In animals in which long-term potentiation was induced by tetanic stimulation, there was a sustained increase in the concentration of glutamate in the perfusate, and, less reliably, in aspartate, as previously reported by Bliss et al. (J. Physiol., Lond. 377, 391-408, 1986) and Errington et al. (Neuroscience 20, 279-284, 1987). The lipoxygenase and phospholipase A2 inhibitor nordihydroguaiaretic acid, when added to the perfusate 30 min before the tetanus, abolished both long-term potentiation of the population excitatory postsynaptic potential and the tetanus-induced increase in glutamate release. Long-term potentiation of the population spike was reduced but not abolished. There was also a sustained increase in the release of arachidonic acid following the induction of long-term potentiation which did not occur when induction was blocked by nordihydroguaiaretic acid. These results are discussed in the light of the possibility that arachidonic acid or one of its lipoxygenase metabolites may be the retrograde messenger which we have postulated is released from postsynaptic sites following tetanic stimulation to trigger increased transmitter release from presynaptic terminals.
在对麻醉大鼠的齿状回进行人工脑脊液灌注的同时，监测由穿通通路刺激诱发的场反应。收集灌注液以分析内源性谷氨酸、天冬氨酸和花生四烯酸。如Bliss等人（《生理学杂志》，伦敦，377卷，391 - 408页，1986年）和Errington等人（《神经科学》，20卷，279 - 284页，1987年）之前所报道的，在通过强直刺激诱导出长时程增强的动物中，灌注液中谷氨酸浓度持续升高，天冬氨酸浓度升高则不太稳定。在破伤风前30分钟将脂氧合酶和磷脂酶A2抑制剂去甲二氢愈创木酸添加到灌注液中，可消除群体兴奋性突触后电位的长时程增强以及破伤风诱导的谷氨酸释放增加。群体峰电位的长时程增强有所降低但未被消除。在长时程增强诱导后，花生四烯酸的释放也持续增加，而当诱导被去甲二氢愈创木酸阻断时则不会出现这种情况。鉴于花生四烯酸或其脂氧合酶代谢产物之一可能是逆行信使这一可能性，对这些结果进行了讨论。我们推测，在强直刺激后，逆行信使从突触后位点释放，以触发突触前终末递质释放增加。
