カルシウム貯蔵庫は,シナプス改変の極性および入力特異性を調節する.
M Nishiyama1, K Hong, K Mikoshiba
1Department of Biology, University of California at San Diego, La Jolla 92093-0357, USA.
Nature
|December 16, 2000
まとめ
活動誘発性シナプス可塑性は,長期増強 (LTP) や抑うつ (LTD) のように,ポストシナプスカルシウムに依存する. 内部貯蔵庫からのカルシウムの流入と放出は,シナプス改変の極性および特異性を調節する.
科学分野:
- 神経科学は神経科学である.
- シナプスの可塑性
- 分子生物学は分子生物学である.
背景:
- 長期増強 (LTP) と長期抑うつ (LTD) を含むシナプス変異は,神経系の発達と可塑性にとって極めて重要です.
- シナプス効果の活動に依存した変化は,学習と記憶に不可欠です.
- 重要な質問は,これらの変更が活性化されたシナプスに限られているかどうかです.
研究 の 目的:
- シナプスの可塑性を調節する際に,シナプスの後のカルシウム流入と内部カルシウム貯蔵の役割を調査する.
- 長期増強 (LTP) と長期抑うつ (LTD) 誘導の入力特異性を決定する.
- 活動誘発シナプス変異の極性および特異性の基礎となるメカニズムを解明する.
主な方法:
- 海馬のCA1領域における電気生理学的記録.
- NMDA (N-メチル-D-アスパルテート) 受容体の薬理学的阻害により,ポストシナプスカルシウム流入を調節する.
- リアノジン受容体とイノシトール三リン酸 (InsP3) 受容体の阻害により,細胞内カルシウム放出を研究する.
- タイプ1のInsP3受容体の遺伝的削除.
主要な成果:
- NMDA受容体の部分封鎖は,LTPをLTDに変換し,ヘテロシナプス入力でLTDを誘導しました.
- ホモシナプス LTD の誘導には,機能的なライアノジン受容体が必要であり,ヘテロシナプス LTD では,InsP3受容体が必要であった.
- リアノジン受容体を遮断すると,ホモシナプス的なLTDは解消されるが,ヘテロシナプス的なLTDは解消されない.
- 1型InsP3受容体の遺伝子削除により,LTDはLTPに変換され,ヘテロシナプスLTDは除去されました.
結論:
- リアノジンとInsP3受容体からの流入と放出の影響を受けるポストシナプスカルシウムは,シナプス変異の方向 (LTP/LTD) と特異性を左右します.
- 細胞内カルシウム貯蔵の微分活性化は,ホモシナプス対ヘテロシナプス可塑性を決定する上で重要な役割を果たします.
- これらの発見は,カルシウムダイナミクスに基づくシナプス可塑性を制御する洗練されたメカニズムを明らかにしています.
関連する概念動画
01:19The Role of Ion Channels in Neuronal Computation
3.2K
A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
3.2K
01:26Chemical Synapses
9.4K
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
9.4K
01:27Feedback Regulation of Calcium Concentration
2.9K
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
2.9K
01:16Calmodulin-dependent Signaling
4.9K
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,...
4.9K
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
4.6K
Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
4.6K
01:26Chemical Synapses
10.8K
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
10.8K