2021 Fiscal Year Final Research Report

Learning-promoted synaptic diversity and a possible encording rule of CA1 pyramidal neurons

Research Project

PDF

Project/Area Number	19H03402
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 48020:Physiology-related
Research Institution	Yamaguchi University
Principal Investigator	Mitsushima Dai 山口大学, 大学院医学系研究科, 教授 (70264603)
Co-Investigator(Kenkyū-buntansha)	西井淳山口大学, 大学院創成科学研究科, 教授 (00242040) 村井礼山口大学, 国際総合科学部, 准教授 (30279111) 石川淳子山口大学, 大学院医学系研究科, 助教 (30570808) 呉本尭日本工業大学, 先進工学部, 教授 (40294657) 崎本裕也山口大学, 大学院医学系研究科, 講師 (40634390) 木田裕之山口大学, 大学院医学系研究科, 講師 (70432739)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	エピソード学習 / AMPA受容体 / GABAA受容体 / super burst / ripple firings / synaptic diversity / memory encoding / entropy
Outline of Final Research Achievements	We acclimated male rats to home cage and allowed them to experience one of the following episodes for 10 min: restraint stress, social contact with a female, social contact with a male, or contact with a novel object, and recorded multiple unit firing activity in the hippocampal CA1 neurons before and after in a freely moving condition. Forty minutes after the experience, the plasticity at excitatory and inhibitory synapses was analyzed using slice patch clamp technique. Although sporadic basal firings were mainly observed before the experience, spontaneous high-frequency firing over 3SD of basal firings occurred many times during and immediately after the experience, followed by numerous firing clusters (ripple firings, approx 50 msec duration). By analyzing the diversity, we found the diversity of spontaneous high-frequency firings, ripple firings, and synaptic diversification were specific to the most recent episodic experience.
Free Research Field	神経生理学
Academic Significance and Societal Importance of the Research Achievements	記銘過程を明らかにできれば、認知症など高次機能疾患モデルと比較し、病態生理の解明や診断法の確立に生かせる。実際、Amyloid beta1-42 oligomerの海馬内投与は、エピソード学習を阻害し、閾値低下による異常発火やCA1シナプスにおけるGABAA受容体単一チャネル電流の低下など様々な病態変化を示した。どの段階でシナプスや発火活動に情報破綻が生じるのか疾患独自の障害発生源を特定し、薬物を用いた治療戦略に活用できると考えられる。