Enhancement of long-term potentiation via muscarinic modulation in the hippocampus of HCNP precursor transgenic mice

Enhancement of long-term potentiation via muscarinic modulation in the hippocampus of HCNP precursor transgenic mice
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DOI:
10.1016/j.neulet.2015.04.028
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发表时间:
2015-06-15
影响因子:
2.5
通讯作者:
Matsukawa, Noriyuki
Matsukawa, Noriyuki
中科院分区:
医学4区
文献类型:
--
作者:
Ohi, Yoshiaki;Kato, Daisuke;Matsukawa, Noriyuki

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海马胆碱能神经刺激肽(HCNP)在体内外通过增加隔核胆碱乙酰转移酶水平来调节隔海马乙酰胆碱的合成。此外,转HCNP-前体蛋白基因(HCNP-pp TG)的小鼠表现出抑郁行为。为了研究HCNP和/或HCNP-pp对海马神经活动的生理作用,我们研究了HCNP-pp的过表达是否增强了海马神经活动的效率。强直刺激小鼠海马片的Schaffer侧支-连合纤维(SCs)可诱发兴奋性突触传递的长时程增强(LTP)。与野生型斜发鼠(WT)相比,HCNP-pp TG小鼠的LTP显著增加。阿托品或哌仑西平可阻断hcnp-pp TG小鼠LTP的这种易化作用,但甲戊胺不能。相反,阿托品不影响WT小鼠的LTP,但氨基甲胆碱却使LTP增强。然而,在场兴奋性突触后电位的输入输出关系和成对脉冲刺激SCs的易化比方面,HCNP-pp Tg小鼠和WT小鼠之间没有差异,表明HCNP-pp Tg小鼠突触前谷氨酸的释放与WT小鼠相似。这些结果提示,M_1对谷氨酸能突触后功能的调节可能参与了增强HCNP-pp TG小鼠的LTP。(C)2015爱思唯尔爱尔兰有限公司。保留所有权利。
Hippocampal cholinergic neurostimulating peptide (HCNP) regulates acetylcholine synthesis in the septal hippocampus through the quantitative increase of choline acetyltransferase levels in the septal nucleus both in vitro and in vivo. Additionally, HCNP-precursor protein transgenic (HCNP-pp Tg) mice display depressive behavior. To examine the physiological function of HCNP and/or HCNP-pp on hippocampal neural activity, we investigated whether overexpression of HCNP-pp strengthened the efficiency of neural activity in the hippocampus. Long-term potentiation (LTP) of excitatory synaptic transmission was induced by a tetanic stimulation of the Schaffer collateral-commissural fibers (SCs) in mouse hippocampal slices. LTP in HCNP-pp Tg mice was significantly enhanced when compared with wild-type littermate (WT) mice. This facilitation of LTP in HCNP-pp Tg mice was blocked by atropine or pirenzepine, but not by mecamylamine. In contrast, LTP in WT mice was not affected by atropine, but enhanced by carbachol. However, neither difference in the input-output relationship of field excitatory postsynaptic potentials nor in the facilitation ratio in paired-pulse stimulation of the SCs was observed between HCNP-pp Tg and WT mice, indicating that presynaptic glutamate release in HCNP-pp Tg mice is similar to that of WT mice. These results suggest that muscarinic (M1) modulation of glutamatergic postsynaptic function may be involved in strengthening LTP in HCNP-pp Tg mice. (C) 2015 Elsevier Ireland Ltd. All rights reserved.