Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Shahid Fahmideh Street, 65178/518, Hamadan, Iran.
Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
BMC Neurosci. 2023 Jan 12;24(1):3. doi: 10.1186/s12868-022-00767-z.
The release of various neurotransmitters and thereby the excitability of neuronal circuits are regulated by the endocannabinoid system in an activity-dependent manner. Hippocampal long-term potentiation (LTP) is augmented in cannabinoid type 1 (CB1) receptor-deficient mice. CB1 receptors exist on GABAergic axon terminals in the hippocampus. In our previous work, we showed that CB1 antagonists increased the population spike (PS) amplitude, field excitatory post-synaptic potential (fEPSP), and the LTP induction in the dentate gyrus (DG) of the rat hippocampus while the GABA antagonist decreased these parameters. Determining the underlying mechanisms of the pre- and/or postsynaptic locus of LTP expression is of great importance. In this study, we investigated whether LTP alteration acutely caused by CB1 and GABA receptor antagonists (AM251 and CGP55845, respectively) happens at the postsynaptic or presynaptic regions, or at both. Therefore, the paired-pulse ratio (PPR) was assessed prior to and following the LTP induction in the studied groups.
Male Wistar rats were randomly assigned to the groups of control, AM251, CGP55845, CGP55845 + AM251. A high-frequency stimulation (HFS) of the perforant path (PP) was used to induce LTP in the DG region.
Statistical analysis revealed that AM251 produced significant increase in excitatory postsynaptic potential (EPSP) slope and amplitude of PS. Conversely, administration of CGP55845 produced decrease in slope of EPSP. The current results indicated that the PPR was not influenced by LTP induction in the presence of AM251 or CGP55845 either alone or their combination.
It can be concluded that the site causing LTP expression is, at least in part, the postsynaptic site because PPR was not influenced by LTP induction in the presence of AM251 or CGP55845 either alone or their combination.
内源性大麻素系统以活动依赖性方式调节各种神经递质的释放，从而调节神经元回路的兴奋性。在大麻素 1 型（CB1）受体缺陷小鼠中，海马长时程增强（LTP）增强。CB1 受体存在于海马的 GABA 能轴突末梢。在我们之前的工作中，我们表明 CB1 拮抗剂增加了大鼠海马齿状回（DG）的群体峰（PS）幅度、场兴奋性突触后电位（fEPSP）和 LTP 诱导，而 GABA 拮抗剂降低了这些参数。确定 LTP 表达的突触前和/或突触后位置的潜在机制非常重要。在这项研究中，我们研究了 CB1 和 GABA 受体拮抗剂（分别为 AM251 和 CGP55845）急性引起的 LTP 改变是否发生在突触后或突触前区域，或者两者都有。因此，在研究组中，在 LTP 诱导之前和之后评估了成对脉冲比（PPR）。
雄性 Wistar 大鼠被随机分配到对照组、AM251 组、CGP55845 组和 CGP55845+AM251 组。使用穿通路径（PP）的高频刺激（HFS）诱导 DG 区的 LTP。
统计分析显示，AM251 可显著增加兴奋性突触后电位（EPSP）斜率和 PS 幅度。相反，CGP55845 的给药导致 EPSP 斜率降低。目前的结果表明，无论单独使用 AM251 或 CGP55845 还是联合使用，PPR 均不受 LTP 诱导的影响。
可以得出结论，导致 LTP 表达的部位至少部分是突触后部位，因为在单独使用 AM251 或 CGP55845 或联合使用时，PPR 不受 LTP 诱导的影响。
