Son H, Lu Y F, Zhuo M, Arancio O, Kandel E R, Hawkins R D
Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Learn Mem. 1998 Jul-Aug;5(3):231-45.
Previous results have suggested that cGMP is involved in hippocampal long-term potentiation (LTP), perhaps as the presynaptic effector of a retrograde messenger. However, other studies have failed to replicate some of those results, making the role of cGMP uncertain. We therefore reexamined this question and identified several variables that can affect the contribution of cGMP. First, brief perfusion with 8-Br-cGMP before weak tetanic stimulation produced long-lasting potentiation in the CA1 region of hippocampal slices, but more prolonged perfusion with 8-Br-cGMP before the tetanus did not produce long-lasting potentiation. Second, the activity-dependent long-lasting potentiation by cGMP analogs was reduced when NMDA receptors were completely blocked, indicating that NMDA receptor activation contributes to, but is not required for, the potentiation. The amount of reduction of the potentiation differed with different protocols, and in some cases could be complete. Third, LTP produced by strong tetanic stimulation in the stratum radiatum of CA1 (which expresses eNOS) was blocked by inhibitors of soluble guanylyl cyclase or cGMP-dependent protein kinase, but LTP in the stratum oriens (which does not express eNOS) was not. The results of these experiments should help to explain some of the discrepant findings from previous studies, and, in addition, may provide insights into the mechanisms and functional role of the cGMP-dependent component of LTP.
先前的研究结果表明，环磷酸鸟苷（cGMP）参与海马体的长时程增强（LTP），可能作为逆行信使的突触前效应器。然而，其他研究未能重复其中一些结果，使得cGMP的作用尚不明确。因此，我们重新审视了这个问题，并确定了几个可能影响cGMP作用的变量。首先，在弱强直刺激前短暂灌注8-溴-cGMP可在海马切片的CA1区产生持久的增强作用，但在强直刺激前更长时间灌注8-溴-cGMP则不会产生持久的增强作用。其次，当NMDA受体被完全阻断时，cGMP类似物的活动依赖性持久增强作用减弱，这表明NMDA受体激活有助于增强作用，但并非其必需条件。增强作用的减弱程度因不同方案而异，在某些情况下可能完全被阻断。第三，在CA1区辐射层（表达内皮型一氧化氮合酶）中由强强直刺激产生的LTP被可溶性鸟苷酸环化酶或cGMP依赖性蛋白激酶的抑制剂所阻断，但在原层（不表达内皮型一氧化氮合酶）中的LTP则未被阻断。这些实验结果应有助于解释先前研究中一些相互矛盾的发现，此外，还可能为LTP的cGMP依赖性成分的机制和功能作用提供见解。
