Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats

作者：Wei Wang, Florian Duclot, Bradley R. Groveman, Nicole Carrier, Haifa Qiao, Xiaoqian Fang, Hui Wang, Wenkuan Xin, Xinghong Jiang, Michael W. Salter, Ding Xin-sheng, Mohamed Kabbaj, Xian‐Min Yu · 发表于：PLoS ONE · 年份：2018 · DOI：10.1371/journal.pone.0195095 · 被引用次数：8 · 研究领域：Neuroscience and Neuropharmacology Research、Memory and Neural Mechanisms、Amino Acid Enzymes and Metabolism

BACKGROUND: Understanding molecular mechanisms underlying the induction of learning and memory impairments remains a challenge. Recent investigations have shown that the activation of group I mGluRs (mGluR1 and mGluR5) in cultured hippocampal neurons by application of (S)-3,5-Dihydroxyphenylglycine (DHPG) causes the regulated internalization of N-methyl-D-aspartate receptors (NMDARs), which subsequently activates protein kinase D1 (PKD1). Through phosphorylating the C-terminals of the NMDAR GluN2 subunits, PKD1 down-regulates the activity of remaining (non-internalized) surface NMDARs. The knockdown of PKD1 does not affect the DHPG-induced inhibition of AMPA receptor-mediated miniature excitatory post-synaptic currents (mEPSCs) but prevents the DHPG-induced inhibition of NMDAR-mediated mEPSCs in vitro. Thus, we investigated the in vivo effects of bilateral infusions of DHPG into the hippocampal CA1 area of rats in the Morris water maze (MWM) and the novel object discrimination (NOD) tests. METHODS: A total of 300 adult male Sprague Dawley rats (250-280 g) were used for behavioral tests. One hundred ninety four were used in MWM test and the other 106 rats in the NOD test. Following one week of habituation to the vivarium, rats were bilaterally implanted under deep anesthesia with cannulas aimed at the CA1 area of the hippocampus (CA1 coordinates in mm from Bregma: AP -3.14; lateral +/-2; DV -3.0). Through implanted cannulas artificial cerebrospinal fluid (ACSF), the group1 mGl...