Zhou Meng-He, Sun Fang-Fang, Xu Chang, Chen Hui-Bin, Qiao Hui, Cai Xiang, Ma Xin-Ming, An Shu-Cheng
College of Life Science, Shaanxi Normal University, 620 West Chang'an Street, Xi'an, Shaanxi 710119, PR China.
The Institute of Neuroscience, the Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang Road, Guangzhou, Guangdong 51030, PR China.
Behav Brain Res. 2019 Jan 1;356:148-155. doi: 10.1016/j.bbr.2018.06.021. Epub 2018 Jun 24.
Serotonin 5-HT1B receptors (5-HT1BRs) are distributed in hippocampal CA1 and play a pivotal role in cognitive function. Activation of 5-HT1BRs regulates synaptic plasticity at the excitatory synapses in the hippocampus. However, the role and its underlying mechanism of 5-HT1BR activation-mediated glutamatergic synaptic plasticity in spatial memory are not fully understood. In this study, spatial memory of Sprague-Dawley (SD) rats was assessed in a Morris water maze after bilateral dorsal hippocampal CA1 infusion of the 5-HT1BR antagonist GR55562 (25 μg/μL) or agonist CP93129 (25 μg/μL). GR55562 did not affect the spatial memory acquisition but significantly increased the target quadrant preference during the memory consolidation probe performed 14 d after the training session, while CP93129 impaired the memory consolidation process. Moreover, GR55562 significantly increased, while CP93129 significantly decreased, the density of dendritic spines on the distal apical dendrites of CA1 pyramidal neurons. Furthermore, western blot experiments indicated that GR55562 significantly increased, but CP93129 significantly reduced, the expression of Kalirin-7 (Kal-7), PSD95, and GluA2/3 subunits of AMPA receptors. Our results suggest that Kal-7 and Kal-7-mediatedalteration of AMPA receptor subtype expression may play crucial roles in the impact of hippocampal CA1 5-HT1BR activation on spatial memory consolidation.
血清素5 - HT1B受体（5 - HT1BRs）分布于海马CA1区，在认知功能中起关键作用。5 - HT1BRs的激活调节海马兴奋性突触的突触可塑性。然而，5 - HT1BR激活介导的谷氨酸能突触可塑性在空间记忆中的作用及其潜在机制尚未完全明确。在本研究中，将5 - HT1BR拮抗剂GR55562（25μg/μL）或激动剂CP93129（25μg/μL）双侧背侧海马CA1注射后，在Morris水迷宫中评估Sprague - Dawley（SD）大鼠的空间记忆。GR55562不影响空间记忆的获取，但在训练后14天进行的记忆巩固探测期间显著增加了目标象限偏好，而CP93129损害了记忆巩固过程。此外，GR55562显著增加，而CP93129显著降低了CA1锥体神经元远端顶端树突上树突棘的密度。此外，蛋白质印迹实验表明，GR55562显著增加，但CP93129显著降低了Kalirin - 7（Kal - 7）、PSD95和AMPA受体的GluA2/3亚基的表达。我们的结果表明，Kal - 7以及Kal - 7介导的AMPA受体亚型表达改变可能在海马CA1区5 - HT1BR激活对空间记忆巩固的影响中起关键作用。
