Thomas M J, O'Dell T J
Department of Physiology, UCLA School of Medicine 90024, USA.
Brain Res. 1995 Oct 9;695(1):45-52. doi: 10.1016/0006-8993(95)00757-h.
In the CA1 region of the hippocampus, the induction of long-term potentiation (LTP) appears to be controlled by a switch-like biochemical process that is persistently activated following metabotropic glutamate receptor (mGLUR) activation. However, the mGLUR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) does not consistently block the induction of LTP, perhaps because the experimental conditions used by some investigators inadvertently activate this 'molecular switch', thereby fulfilling the requirement for mGLUR activation and rendering LTP insensitive to the effects of mGLUR antagonists. In mouse hippocampal slices we observed that MCPG does not block LTP induced by high-frequency stimulation, Moreover, stimulation protocols designed to deactivate an inadvertently activated molecular switch had no effect on the inability of MCPG to block LTP. MCPG (through a switch-independent mechanism) did inhibit the induction of LTP by a weak induction protocol. Our results thus suggest that MCPT-sensitive mGLURs are not required for the induction of LTP and that a mLGUR-activated 'molecular switch' does not explain the inconsistent effects of MCPG on LTP. Instead, MCPG-sensitive mGLURs may have a modulatory role in the induction of LTP that is most evident when LTP is induced by near threshold patterns of synaptic stimulation.
在海马体的CA1区域，长时程增强（LTP）的诱导似乎受一种类似开关的生化过程控制，该过程在代谢型谷氨酸受体（mGLUR）激活后持续被激活。然而，mGLUR拮抗剂（RS）-α-甲基-4-羧基苯基甘氨酸（MCPG）并不能始终如一地阻断LTP的诱导，这可能是因为一些研究者所采用的实验条件无意中激活了这个“分子开关”，从而满足了mGLUR激活的要求，并使LTP对mGLUR拮抗剂的作用不敏感。在小鼠海马体切片中，我们观察到MCPG并不阻断高频刺激诱导的LTP。此外，旨在使无意中被激活的分子开关失活的刺激方案，对MCPG无法阻断LTP的情况没有影响。MCPG（通过一种不依赖开关的机制）确实能抑制弱诱导方案诱导的LTP。因此，我们的结果表明，LTP的诱导不需要MCPT敏感的mGLURs，并且mLGUR激活的“分子开关”并不能解释MCPG对LTP的不一致作用。相反，MCPG敏感的mGLURs可能在LTP的诱导中具有调节作用，当LTP由接近阈值的突触刺激模式诱导时，这种作用最为明显。
