Riedel G, Casabona G, Reymann K G
Department of Neurophysiology, Institute for Neurobiology, Magdeburg, Germany.
J Neurosci. 1995 Jan;15(1 Pt 1):87-98. doi: 10.1523/JNEUROSCI.15-01-00087.1995.
Metabotropic glutamate receptors (mGluRs) are critically involved in the maintenance of long-term potentiation (LTP) (Reymann and Matthies, 1989; Behnisch et al., 1991; Izumi et al., 1991; Bashir et al., 1993). In order to assess further the physiological role of MGluRs in LTP, we injected freely moving rats with the recently available, competitive mGluR antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (MCPG) intraventricularly and recorded extracellularly the population spike (PS) as well as the field excitatory postsynaptic potential (fEPSP) of the granule cells of the dentate gyrus in response to stimulation of fibers of the perforant path. MCPG was administered in two concentrations (A = 20 mM/5 microliters; B = 200 mM/5 microliters) either 30 min prior to or 5 min after LTP induction. Sodium chloride infusion served as a control. Normal synaptic transmission was not altered by MCPG. However, the mGluR antagonist inhibited LTP in a concentration-dependent manner. Concentration A did not influence the potentiation shortly after the tetanus. In the PS, short-term potentiation (STP), which is decremental in its time course, occurred normally, but in contrast to controls the potentiation declined back to baseline values after 2-3 hr. This dose also reduced the posttetanic increase in the slope function of the fEPSP, and led to a time course of potentiation similar to that for the PS. Concentration B completely abolished the tetanus-induced potentiation. This block was similar to that obtained for the NMDA antagonist 2-amino-5-phosphonopentanoate (AP5). Both MCPG concentrations had no influence on the time course of preestablished LTP. These effects seem to be due to the action of the (+)-isomer of MCPG, since intracerebroventricular application of the (-)-isomer was without effect on the duration and magnitude of LTP. In addition, we were interested in the mGluR subtypes involved in the blocking mechanism of MCPG. 1S,3R-aminocyclopentane-1,3-dicarboxic acid (ACPD)-activated PPI hydrolysis in hippocampal slices was competitively inhibited by MCPG at a concentration of 1 mM or higher. In contrast, this concentration of MCPG did not affect the reduction of forskolin-stimulated cAMP formation by ACPD. These results corroborate recent findings that mGluRs are required for the induction of LTP in CA1 and CA3 in vitro (Bashir et al., 1993; Sergueeva et al., 1993) and in vivo (Riedel and Reymann, 1993). The process of STP is found to be independent of mGluR activation.(ABSTRACT TRUNCATED AT 400 WORDS)
代谢型谷氨酸受体（mGluRs）在长时程增强（LTP）的维持中起关键作用（Reymann和Matthies，1989年；Behnisch等人，1991年；Izumi等人，1991年；Bashir等人，1993年）。为了进一步评估mGluRs在LTP中的生理作用，我们向自由活动的大鼠脑室内注射了最近可得的竞争性mGluR拮抗剂（R,S）-α-甲基-4-羧基苯甘氨酸（MCPG），并在细胞外记录齿状回颗粒细胞的群体峰电位（PS）以及在刺激穿通路径纤维时的场兴奋性突触后电位（fEPSP）。MCPG以两种浓度（A = 20 mM/5微升；B = 200 mM/5微升）在LTP诱导前30分钟或诱导后5分钟给药。输注氯化钠作为对照。MCPG未改变正常的突触传递。然而，mGluR拮抗剂以浓度依赖的方式抑制LTP。浓度A在强直刺激后不久不影响增强作用。在PS中，时程递减的短时程增强（STP）正常发生，但与对照组不同的是，增强作用在2 - 3小时后回落到基线值。该剂量还降低了强直刺激后fEPSP斜率函数的增加，并导致类似于PS的增强时程。浓度B完全消除了强直刺激诱导的增强作用。这种阻断类似于用NMDA拮抗剂2-氨基-5-膦酰戊酸（AP5）所获得的阻断。两种MCPG浓度对预先建立的LTP时程均无影响。这些作用似乎是由于MCPG的（+）-异构体的作用，因为脑室内应用（-）-异构体对LTP的持续时间和幅度没有影响。此外，我们对参与MCPG阻断机制的mGluR亚型感兴趣。1S,3R-氨基环戊烷-1,3-二羧酸（ACPD）在海马切片中激活的PPI水解在浓度为1 mM或更高时被MCPG竞争性抑制。相反，该浓度的MCPG不影响ACPD对福斯高林刺激的cAMP形成的降低。这些结果证实了最近的发现，即mGluRs在体外（Bashir等人，1993年；Sergueeva等人，1993年）和体内（Riedel和Reymann，1993年）CA1和CA3区LTP的诱导中是必需的。发现STP过程独立于mGluR激活。（摘要截短至400字）
