Zhuo M, Small S A, Kandel E R, Hawkins R D
Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY.
Science. 1993 Jun 25;260(5116):1946-50. doi: 10.1126/science.8100368.
Nitric oxide (NO) and carbon monoxide (CO) may act as retrograde messages for long-term potentiation (LTP) in the hippocampus. Zinc protoporphyrin IX, an inhibitor of the enzyme that produces CO, blocked induction of LTP in the CA1 region of hippocampal slices. Application of either NO or CO to slices produced a rapid and long-lasting increase in the size of evoked synaptic potentials if, and only if, the application occurred at the same time as weak tetanic stimulation. This long-term enhancement was spatially restricted to synapses from active presynaptic fibers and appeared to involve mechanisms utilized by LTP, occluding the subsequent induction of LTP by strong tetanic stimulation. The enhancement by NO and CO was not blocked by an N-methyl-D-aspartate (NMDA) receptor blocker, suggesting that NO and CO act downstream from the NMDA receptor. Also, CO produced long-term enhancement when paired with low-frequency stimulation. These results are consistent with the hypothesis that NO and CO, either alone or in combination, serve as retrograde messages that produce activity-dependent presynaptic enhancement during LTP.
一氧化氮（NO）和一氧化碳（CO）可能作为海马体中长时程增强（LTP）的逆行信使。锌原卟啉IX是一种产生CO的酶的抑制剂，它能阻断海马体切片CA1区LTP的诱导。仅当在弱强直刺激同时施加NO或CO时，将其施加到切片上会使诱发的突触电位大小迅速且持久地增加。这种长期增强在空间上局限于来自活跃突触前纤维的突触，并且似乎涉及LTP所利用的机制，从而阻止了随后强强直刺激对LTP的诱导。NO和CO的增强作用不会被N-甲基-D-天冬氨酸（NMDA）受体阻滞剂阻断，这表明NO和CO在NMDA受体的下游起作用。此外，CO与低频刺激配对时会产生长期增强作用。这些结果与以下假设一致：NO和CO单独或联合作用，作为逆行信使，在LTP期间产生依赖于活动的突触前增强。
