Abstract

The type 4 serotonin receptor (5-HT₄R) is highly involved in cognitive processes such as learning and memory. Behavioral studies have shown a beneficial effect of its activation and conversely reported memory impairments by its blockade. However, how modulation of 5HT₄R enables modifications of hippocampal synaptic plasticity remains elusive. To shed light on the mechanisms at work, we investigated the effects of the 5-HT₄R agonist RS67333 on long-term potentiation (LTP) within the hippocampal CA1 area. Although high-frequency stimulation-induced LTP remained unaffected by RS67333, the magnitude of LTP induced by theta-burst stimulation was significantly decreased. This effect was blocked by the selective 5-HT₄R antagonist RS39604. Further, 5-HT₄R-induced decrease in LTP magnitude was fully abolished in the presence of bicuculline, a GABA_AR antagonist; hence, demonstrating involvement of GABA neurotransmission. In addition, we showed that the application of a GABA_BR antagonist, CGP55845, mimicked the effect of 5-HT₄R activation, whereas concurrent application of CGP55845 and RS67333 did not elicit an additive inhibition effect on LTP. To conclude, through investigation of theta burst induced functional plasticity, we demonstrated an interplay between 5-HT₄R activation and GABAergic neurotransmission within the hippocampal CA1 area.

中文翻译：

---

CA1 海马突触可塑性中 5-HT4 受体和 GABA 能系统之间的相互作用。

摘要

4 型血清素受体 (5-HT ₄ R) 高度参与认知过程，例如学习和记忆。行为研究显示了其激活的有益效果，并相反报告了其阻断导致的记忆障碍。然而，5HT ₄ R 的调制如何使海马突触可塑性的改变仍然难以捉摸。为了阐明工作机制，我们研究了 5-HT ₄ R 激动剂 RS67333 对海马 CA1 区域内的长期增强 (LTP) 的影响。尽管高频刺激诱导的 LTP 不受 RS67333 的影响，但由 theta-burst 刺激诱导的 LTP 幅度显着降低。这种效应被选择性 5-HT ₄阻断R拮抗剂RS39604。此外，在荷包牡丹碱（一种 GABA _A R 拮抗剂）存在下，5-HT ₄ R 诱导的 LTP 量级降低被完全消除。因此，证明 GABA 神经传递的参与。此外，我们发现 GABA _B R 拮抗剂 CGP55845的应用模拟了 5-HT ₄ R 激活的作用，而同时应用 CGP55845 和 RS67333 并没有引起对 LTP 的加性抑制作用。总之，通过对θ爆发诱导的功能可塑性的研究，我们证明了海马CA1区域内5-HT ₄ R激活和GABA能神经传递之间的相互作用。