Zhuo M, Kandel E R, Hawkins R D
Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY.
Neuroreport. 1994 May 9;5(9):1033-6. doi: 10.1097/00001756-199405000-00004.
Nitric oxide (NO) has been suggested to play the role of retrograde messenger during long-term potentiation (LTP) in hippocampus. In support of this idea, NO induces LTP when paired with a weak tetanus (50 Hz). An additional criterion that has been proposed for NO being a retrograde messenger is that it should also elicit long-lasting enhancement when paired with low-frequency stimulation of the presynaptic fibers. In the present study, we have tested this prediction. We find that NO produces long-lasting depression rather than potentiation when paired with low-frequency stimulation (0.25 Hz). A similar long-lasting depression is produced by 8-Br-cGMP, a cGMP analog, suggesting that NO may produce its effect by activating soluble guanylyl cyclase. These results demonstrate that NO and cGMP modulate synaptic transmission in the hippocampus by frequency-dependent mechanisms, and suggest that NO is most suitable as a retrograde messenger for LTP when the presynaptic neuron fires at high frequencies. By contrast, carbon monoxide (CO) elicits long lasting enhancement at both low and high frequencies.
一氧化氮（NO）被认为在海马体的长时程增强（LTP）过程中充当逆行信使。支持这一观点的是，当与弱强直刺激（50赫兹）配对时，NO可诱导LTP。对于NO作为逆行信使提出的另一个标准是，当与突触前纤维的低频刺激配对时，它也应引发持久增强。在本研究中，我们测试了这一预测。我们发现，当与低频刺激（0.25赫兹）配对时，NO产生的是持久抑制而非增强。一种环磷酸鸟苷（cGMP）类似物8-溴-cGMP也产生类似的持久抑制，这表明NO可能通过激活可溶性鸟苷酸环化酶发挥其作用。这些结果表明，NO和cGMP通过频率依赖性机制调节海马体中的突触传递，并表明当突触前神经元高频放电时，NO最适合作为LTP的逆行信使。相比之下，一氧化碳（CO）在低频和高频时均引发持久增强。
