title: Enhancement of long-term potentiation via muscarinic modulation in the hippocampus of HCNP precursor transgenic mice.
abstract: 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.
authors.affiliation: Laboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohi
authors.affiliation: Department of Neurology, School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-ku, Nagoya 467-8602, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kato
authors.affiliation: Department of Neurology, School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-ku, Nagoya 467-8602, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Department of Neurology, School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-ku, Nagoya 467-8602, Japan.
authors.forename: Toyohiro
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Neurology, School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-ku, Nagoya 467-8602, Japan.
authors.forename: Yoshino
authors.initials: Y
authors.lastname: Ueki
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Repair, University of South Florida, Tampa, Florida, USA.
authors.forename: Cesario V
authors.initials: CV
authors.lastname: Borlongan
authors.affiliation: Department of Neurology, School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-ku, Nagoya 467-8602, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Ojika
authors.affiliation: Laboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Haji
authors.affiliation: Department of Neurology, School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-ku, Nagoya 467-8602, Japan. Electronic address: norim@med.nagoya-cu.ac.jp.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Matsukawa
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009415:Nerve Net; D009479:Neuropeptides / Q000378:metabolism; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics* / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*
chemical_list: D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009479:Neuropeptides; D049488:Phosphatidylethanolamine Binding Protein; D043643:Receptor, Muscarinic M1; C075274:hippocampal cholinergic neurostimulating peptide
keywords: Hippocampal cholinergic neurostimulating peptide; Hippocampal cholinergic neurostimulating peptide precursor protein; Long-term potentiation; Muscarinic ACh receptor; Phosphatidylethanolamine binding protein