Izumi Y, Zorumski C F
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Synapse. 1999 Mar 1;31(3):196-202. doi: 10.1002/(SICI)1098-2396(19990301)31:3<196::AID-SYN4>3.0.CO;2-K.
We previously found a reduction in the ability of a single 100 Hz x 1 sec tetanus to induce long-term potentiation (LTP) in the CA1 region of hippocampal slices prepared from adult animals. To determine whether this reduction in LTP generation results from changes in neuromodulator function, we examined the ability of several neuromodulators to promote LTP in slices prepared from mature rats. Although acetylcholine, N-methyl-D-aspartate, and an agonist at metabotropic glutamate receptors failed to promote LTP, administration of norepinephrine allowed robust LTP. The effects of norepinephrine were mimicked by an alpha1-adrenergic agonist and were blocked by an alpha1-receptor antagonist. Beta-adrenergic agonists and antagonists were ineffective. These results suggest that norepinephrine acting via alpha1-adrenoceptors may be an important cofactor in promoting lasting synaptic plasticity in the adult central nervous system and that changes in adrenergic function may contribute to maturation- or aging-associated changes in memory function.
我们之前发现，单次100赫兹×1秒的强直刺激诱导成年动物制备的海马脑片CA1区产生长时程增强（LTP）的能力有所下降。为了确定LTP产生的这种下降是否源于神经调质功能的变化，我们检测了几种神经调质在成熟大鼠制备的脑片中促进LTP的能力。尽管乙酰胆碱、N-甲基-D-天冬氨酸和促代谢型谷氨酸受体激动剂未能促进LTP，但给予去甲肾上腺素可使LTP显著增强。去甲肾上腺素的作用可被α1-肾上腺素能激动剂模拟，并被α1-受体拮抗剂阻断。β-肾上腺素能激动剂和拮抗剂则无效。这些结果表明，通过α1-肾上腺素能受体发挥作用的去甲肾上腺素可能是促进成年中枢神经系统持久突触可塑性的重要辅助因子，并且肾上腺素能功能的变化可能导致与成熟或衰老相关的记忆功能变化。
