Npas4は,文脈的な記憶形成に必要なCA3の転写プログラムを調節する
Kartik Ramamoorthi1, Robin Fropf, Gabriel M Belfort
1McGovern Institute for Brain Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|December 24, 2011
まとめ
転写因子Npas4は,海馬における文脈的な記憶の形成に不可欠である. CA3領域におけるその活動は,記憶のエンコーディングとリコールに不可欠な遺伝子を調節する.
科学分野:
- 神経科学は神経科学である.
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
背景:
- ヒポキャンプスのCA3領域は,迅速な文脈的な記憶のエンコーディングに不可欠です.
- この過程の根底にある特定の遺伝的メカニズムは完全に理解されていません.
研究 の 目的:
- CA3依存の文脈記憶形成における活動依存の転写因子Npas4の役割を調査する.
- CA3.3におけるNpas4によって調節される転写プログラムを識別する.
主な方法:
- Npas4.4のグローバル・ノックアウトと選択的なCA3削除モデルを利用した.
- これらのモデルで文脈的なメモリパフォーマンスを評価した.
- 分析されたNpas4表現パターンのポスト文脈学習.
- RNAポリメラーゼIIの募集を含む,Npas4の作用機構を調査した.
主要な成果:
- Npas4の発現は,文脈学習によるCA3に特異的に誘発された.
- 全局的なNpas4ノックアウトとCA3固有の削除の両方が,文脈的な記憶を損ねました.
- CA3におけるNpas4の復元は,ノックアウトマウスにおける記憶の欠陥を回復させた.
- Npas4はRNAポリメラーゼIIを誘導して,遺伝子プロモーターや増強剤を標的にすることが示された.
結論:
- Npas4は,CA3.3における活動に依存した転写プログラムの主調節体として作用する.
- このNpas4を媒介するプログラムは,文脈的な記憶形成に不可欠です.
- Npas4は,記憶の分子機構において中心的な役割を果たしています.
さらに関連する動画
12:30Production of Nurr-1 Specific Polyclonal Antibodies Free of Cross-reactivity Against Its Close Homologs, Nor1 and Nur77
Published on: August 17, 2015
10:03Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins
Published on: August 10, 2014
関連する概念動画
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:25Long-term Potentiation
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Hebbian LTP
LTP can occur when presynaptic neurons...
Hebbian LTP
LTP can occur when presynaptic neurons...
01:35Long-term Potentiation
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre- and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
01:58Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...