Ohi Yoshiaki, Kato Daisuke, Mizuno Masayuki, Sato Toyohiro, Ueki Yoshino, Borlongan Cesario V, Ojika Kosei, Haji Akira, Matsukawa Noriyuki
Laboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650, Japan.
Department of Neurology, School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-ku, Nagoya 467-8602, Japan.
Neurosci Lett. 2015 Jun 15;597:1-6. doi: 10.1016/j.neulet.2015.04.028. Epub 2015 Apr 18.
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.
海马胆碱能神经刺激肽（HCNP）在体外和体内均可通过增加隔核中胆碱乙酰转移酶水平的数量来调节隔海马中的乙酰胆碱合成。此外，HCNP前体蛋白转基因（HCNP-pp Tg）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功能，我们研究了HCNP-pp的过表达是否增强了海马中神经活动的效率。通过对小鼠海马切片中的Schaffer侧支-连合纤维（SCs）进行强直刺激来诱导兴奋性突触传递的长时程增强（LTP）。与野生型同窝小鼠（WT）相比，HCNP-pp Tg小鼠的LTP显著增强。HCNP-pp Tg小鼠中LTP的这种促进作用被阿托品或哌仑西平阻断，但不受美加明阻断。相反，WT小鼠中的LTP不受阿托品影响，但被卡巴胆碱增强。然而，在HCNP-pp Tg小鼠和WT小鼠之间，未观察到场兴奋性突触后电位的输入-输出关系或SCs配对脉冲刺激中的促进率有差异，这表明HCNP-pp Tg小鼠中突触前谷氨酸释放与WT小鼠相似。这些结果表明，毒蕈碱（M1）对谷氨酸能突触后功能的调节可能参与增强HCNP-pp Tg小鼠中的LTP。
