Department of Neurology, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu, Gifu 501-1196, Japan.
Int J Mol Sci. 2019 Oct 28;20(21):5367. doi: 10.3390/ijms20215367.
The cholinergic efferent network from the medial septal nucleus to the hippocampus has an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to efficiently encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP) induces acetylcholine synthesis in medial septal nuclei. HCNP is processed from the N-terminal region of a 186 amino acid, 21 kD HCNP precursor protein called HCNP-pp (also known as Raf kinase inhibitory protein (RKIP) and phosphatidylethanolamine-binding protein 1 (PEBP1)). In this study, we generated HCNP-pp knockout (KO) mice and assessed their cholinergic septo-hippocampal projection, local field potentials in CA1, and behavioral phenotypes. No significant behavioral phenotype was observed in HCNP-pp KO mice. However, theta power in the CA1 of HCNP-pp KO mice was significantly reduced because of fewer cholineacetyltransferase-positive axons in the CA1 stratum oriens. These observations indicated disruption of cholinergic activity in the septo-hippocampal network. Our study demonstrates that HCNP may be a cholinergic regulator in the septo-hippocampal network.
从内侧隔核到海马的胆碱能传出网络在学习和记忆过程中起着重要作用。这种胆碱能投射可以在海马体中产生θ振荡，从而有效地编码新信息。海马胆碱能神经刺激肽（HCNP）诱导内侧隔核中的乙酰胆碱合成。HCNP 是由一种 186 个氨基酸、21 kD 的 HCNP 前体蛋白（称为 HCNP-pp，也称为 Raf 激酶抑制蛋白（RKIP）和磷脂酰乙醇胺结合蛋白 1（PEBP1））的 N 端区域加工而来。在这项研究中，我们生成了 HCNP-pp 敲除（KO）小鼠，并评估了它们的胆碱能隔海马投射、CA1 局部场电位和行为表型。在 HCNP-pp KO 小鼠中未观察到明显的行为表型。然而，由于 CA1 层状或iens 中的胆碱乙酰转移酶阳性轴突减少，HCNP-pp KO 小鼠的 CA1 中的θ功率显著降低。这些观察结果表明，隔海马网络中的胆碱能活动受到干扰。我们的研究表明，HCNP 可能是隔海马网络中的一种胆碱能调节剂。
