Synaptotagmin1 synthesis induced by synaptic plasticity in mouse hippocampus through activation of nicotinic acetylcholine receptors

• Published in: Neuroscience letters Vol. 489; no. 1; pp. 25 - 29
• Main Authors: Nishimoto, Takaaki, Kadoyama, Keiichi, Taniguchi, Taizo, Takano, Masaoki, Otani, Mieko, Nakamura-Hirota, Tooru, Lu, Yabin, Matsumoto, Akira, Matsuyama, Shogo
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.02.2011; Elsevier
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Hippocampus - metabolism; Long-term potentiation (LTP); Long-Term Potentiation - physiology; Male; Mice; Mice, Inbred C57BL; Nicotine; Receptors, Nicotinic - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Synaptotagmin I - biosynthesis; Synaptotagmin I - genetics; Vertebrates: nervous system and sense organs; α4β2 nAChR; α7 nAChR; α7 nAChR; α4β2 nAChR; Long-term potentiation (LTP); Nicotine; Rodentia; Central nervous system; Encephalon; Vertebrata; Cholinergic receptor; Mammalia; Mouse; Animal; Synaptic plasticity; Nicotinic receptor; Hippocampus
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2010.11.059

▶ Nicotinic agonists express a LTP-like facilitation in vivo in mouse hippocampus. ▶ Nicotine increases Syt1 mRNA level during LTP-like facilitation in hippocampus. ▶ Nicotine increases SYT1 protein level during LTP-like facilitation in hippocampus. ▶ Nicotine-enhanced SYT1 protein are mediated by activation of α7 and/or α4β2 nAChRs. We have reported that systemic application of nicotinic agonists expresses a long-term potentiation (LTP)-like facilitation, a model of synaptic plasticity, in vivo in the mouse hippocampus. The present study conducted to clarify the involvement of synaptotagmin1 in synaptic plasticity by investigating the time-dependent change of the mRNA and protein levels of synaptotagmin1 during LTP-like facilitation in the mouse hippocampus. The mRNA expression of synaptotagmin1 increased during 2- to 8-h period by intraperitoneal application of nicotine (3 mg/kg), returning to the basal level in 12-h. Also, the protein level of synaptotagmin1, but not synaptophysin, in a total fraction from hippocampus increased during 4- to 12-h period by the same treatment, returning to the basal level in 24-h. The protein level of synaptotagmin1 in a membrane fraction from hippocampus also increased during 4- to 8-h period by nicotine, returning to the basal level in 12-h. This nicotine-enhanced synaptotagmin1 protein in a membrane fraction was inhibited by pretreatment of mecamylamine (0.3 mg/kg, i.p.), a nonselective nicotinic acetylcholine receptors (nAChRs) antagonist. Furthermore, choline (30 mg/kg, i.p.), a selective α7 nAChR agonist, or ABT-418 (10 mg/kg, i.p.), a selective α4β2 nAChR agonist, enhanced the level of synaptotagmin1 in a membrane fraction. Our findings demonstrate that synaptotagmin1 protein following mRNA which is enhanced without increasing the number of synapse gathers around pre-synaptic membrane during hippocampal LTP-like facilitation through activation of α7 and/or α4β2 nAChRs in the brain. These results suggest that new-synthesized synaptotagmin1 following synaptic plasticity may contribute to long-lasting synaptic plasticity via positive, feedfoward mechanisms.