Name: synaptic pruning in long-term depression
Uploaded: 2019-03-11T09:21:27.000Z
Duration: 1 min 5 s
Channel: JoVE

ナレーター]長期抑圧、またはLTDは 機能低下を伴うシナプス可塑性のプロセスで シナプス前ニューロンの結合とシナプス後ニューロンの結合の間で起こります LTDが起こる仕組みの一つは シナプス前の刺激の後シナプス後ニューロンに流入する カルシウムイオンの量に依存しています。シナプス前の低頻度な刺激に起因してカルシウム濃度が低いと 最終的にエンドサイトーシスを起こすシグナルカスケードを 引き起こすか、または膜組織から AMPAグルタミン酸塩受容体を除去する場合があります 結果、散発的な同様のシナプス前の刺激に対する シナプス後の反応は さらに低下します LTDが学習にとって重要な理由は ほとんどまたは全く使われないシナプスの 反応を低下または除去すら行うからです リソースや空間は整理され 他の機能のために神経を利用できます 重要度の高いシナプスを増強するLTPなどが挙げられます

Kukushkin, Nikolay Vadimovich, and Thomas James Carew. "Memory Takes Time." Neuron 95, no. 2 (2017年7月19日): 259–79.[<a href="https://doi.org/10.1016/j.neuron.2017.05.029" target="__blank">ソース</a>]

「NMDA受容体依存性長期増強および長期うつ病(LTP / LTD)」 Cold Spring Harbor Perspectives in Biology 4、no. 6(2012年6月1日):a005710。[<a href="https://doi.org/10.1101/cshperspect.a005710" target="__blank">ソース</a>]

長期抑圧

長期抑圧（LTD）は、脳内でシナプス可塑性（化学的なシナプスの強さを変化させること）が生じる方法のひとつです。LTDとは、シナプス前部とシナプス後部の神経結合の間で、時間の経過とともにシナプスが弱くなっていくプロセスです。LTDによるシナプスの弱体化は、長期増強（LTP）によるシナプスの強化と相反する働きをし、学習と記憶を支える主要なメカニズムとなっています。 
 
 <h4>カルシウムイオン濃度のメカニズム</h4>
 
 すべてのシナプスがLTPなどによって最大限に強化されると、脳の効率は頭打ちになり、学習や新しい記憶の形成が難しくなります。LTDは、弱ったシナプスを縮小して資源を確保し、中枢神経系に柔軟性を取り戻す方法です。LTDが起こるメカニズムの1つは、シナプス前部の刺激を受けた後、シナプス後部の神経細胞内にあるカルシウムイオンの数によります。シナプス前の刺激が少ないと、カルシウムイオンの流入量が少なくなり、その結果、シナプス後の神経細胞内のカルシウムイオン濃度が低くなります。 
 
 カルシウムイオン濃度が低下すると、シグナルカスケードが始まり、グルタミン酸受容体（AMPA）が細胞膜からエンドサイトーシスまたは除去されます。その結果、正の電荷を帯びたイオンが入り込み、膜を脱分極させるチャネルが少なくなるため、同じ散発的なシナプス前刺激に対するシナプス後の反応はさらに弱くなるのです。ニューロンは、AMPA受容体を後から再利用したり、構成するサブユニットに分離したりします。
 
 LTDは、最初に海馬で起こると報告され、古い記憶を消去すると考えられていました。その後、小脳、線条体、大脳皮質など、多くの脳領域でLTDが起こることが明らかになりました。LTDがどこにでも存在することは、脳の機能を正常に保つために重要であることを示しています。
 
 <h4>LTDと病気</h4>
 
 LTDの機能不全は、依存症、精神遅滞、アルツハイマー病など、多くの神経疾患や認知疾患の原因になると考えられています。現在、LTDのメカニズムや神経疾患の発生メカニズムを解明し、治療法を開発するための研究が進められています。

長期うつ病(LTD)は、シナプス可塑性(化学シナプスの強度の変化)が...

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Long-term Depression

synaptic pruning in long-term depression

Long-term depression, or LTD, is a form of synaptic plasticity that weakens chemical synapses over time. It acts between presynaptic and postsynaptic neurons. LTD works in opposition to long-term potentiation, or LTP, which strengthens synapses. Together, LTD and LTP are two of the main mechanisms behind learning and memory.

LTD helps the brain avoid staying locked in a fully strengthened state. If synapses were always maximally strengthened, the brain would become less efficient and it would be harder to learn new information or form new memories. By weakening weaker synapses, LTD helps prune connections and restore flexibility to the central nervous system.

One common LTD mechanism depends on calcium ions in the postsynaptic neuron after presynaptic stimulation. When presynaptic activity is infrequent or low, calcium ion influx is also low. This leads to a low calcium ion concentration in the postsynaptic cell. That signal starts a cascade that removes AMPA glutamate receptors from the plasma membrane through endocytosis.

With fewer AMPA receptors on the membrane, the postsynaptic response to the same weak presynaptic signal becomes even smaller. Fewer channels are available for positively charged ions to enter and depolarize the membrane. The neuron can later reuse these AMPA receptors or break them into subunits.

LTD was first described in the hippocampus, where it is thought to help clear old memories. It has also been found in the cerebellum, striatum, and cortex. Because LTD appears in many brain regions, it is an important part of normal brain function. Problems with LTD are thought to play a role in addiction, mental retardation, and Alzheimer’s disease, so researchers continue to study it and possible treatments.

Synaptic Pruning in Long-term Depression

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Long-term potentiation, or LTP, is a form of synaptic strengthening in the brain. It changes the strength of chemical synapses over time between pre- and postsynaptic neurons. LTP works against long-term depression, or LTD, which weakens synapses. Together, LTP and LTD are major mechanisms behind learning and memory. LTP can happen when a presynaptic neuron fires again and again and keeps stimulating a postsynaptic neuron. This is called Hebbian LTP, based on Donald Hebb’s idea that neurons...

long-term depression

Long-term depression, or LTD, is a form of synaptic plasticity that weakens chemical synapses over time. It acts between presynaptic and postsynaptic neurons. LTD works in opposition to long-term potentiation, or LTP, which strengthens synapses. Together, LTD and LTP are two of the main mechanisms behind learning and memory. LTD helps the brain avoid staying locked in a fully strengthened state. If synapses were always maximally strengthened, the brain would become less efficient and it would...

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Learn how long-term depression weakens synapses, removes AMPA receptors, and supports learning, memory, and brain flexibility in high school biology.

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Synaptic Pruning in Long-term Depression

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