Name: synaptic strengthening in learning and memory
Uploaded: 2025-10-23T11:49:27.000Z
Duration: 1 min 35 s
Channel: JoVE

長期増強(LTP)は，シナプス前とシナプス後のニューロン結合の間に 時間の経過とともに起こるシナプス強化のプロセスです。1つのプロセスのなかで，シナプス前ニューロンが シナプス後細胞を繰り返し刺激すると，シナプス後膜におけるイオンチャネルの種類や数の変化，例えばＮ-メチル-Ｄ-アスパラギン酸(NMDA)という グルタミン酸受容体への変化を引き起こします。NMDA受容体は通常マグネシウムイオンによって不活性化されますが，反復刺激による強い脱分極により、マグネシウムイオンは置換されて カルシウムイオンが入れるようになります。このカルシウム流入は、第二のグルタミン酸受容体に達するシグナル伝達カスケードが開始します。アルファアミノ3ヒドロキシ5 メチル4イソキサゾリルプロピオン酸 が，膜に挿入されます。この場合、より多くの陽イオンがニューロンに流れ込み、シナプス前刺激に対して シナプス後反応が強くなります。LTPは学習に不可欠であり、継続は力なり」ということわざを裏づけるものです。シナプス前刺激が持続する場合、新しく強化された反応は数分から数週間以上続くため、継続は力なり」となるわけです。

ニコル、ロジャーA.「長期増強の簡単な歴史」 ニューロン93、第2号(2017年1月18日):281-90。[<a href="https://doi.org/10.1016/j.neuron.2016.12.015" target="__blank">ソース</a>]

Bliss, T. V. P., G. L. Collingridge, and R. G. M. Morris. "Synaptic Plasticity in Health and Disease: Introduction and Overview." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1633 (2014年1月5日).[<a href="https://doi.org/10.1098/rstb.2013.0129" target="__blank">ソース</a>]

長期増強

長期増強（LTP）は、脳におけるシナプス可塑性（化学的なシナプスの強さを変化させること）の方法の一つです。LTPは、シナプス前とシナプス後の神経結合の間で時間をかけて起こるシナプス強化のプロセスです。LTPによるシナプスの強化は、長期抑圧（LTD）によるシナプスの弱化と相反する働きをし、共に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>Hebb型LTP </h4>
 
 シナプス前の神経細胞が繰り返し発火し、シナプス後の神経細胞を刺激するとLTPが起こします。これは、1949年にドナルド・ヘッブ（Donald Hebb）が提唱した「一緒に発火したニューロンは一緒に配線される」という仮説に基づいており、Hebb型LTPと呼ばれています。シナプス前のニューロンが繰り返し刺激を受けることで、シナプス後の膜にあるイオンチャネルの種類と数が変化します。
 
 興奮性神経伝達物質であるグルタミン酸のシナプス後受容体には、N-メチル-D-アスパラギン酸（NMDA）受容体と、α-アミノ-3-ヒドロキシ-5-メチル-4-イソオキサゾールプロピオン酸（AMPA）受容体の2種類があり、LTPに関与しています。NMDA受容体は、グルタミン酸が結合すると開口しますが、通常はマグネシウムイオンによって孔が塞がれており、他の正電荷を帯びたイオンが神経細胞内に侵入するのを防いでいます。しかし、シナプス前の神経細胞から放出されたグルタミン酸は、シナプス後のAMPA受容体に結合し、ナトリウムイオンの流入を引き起こし、膜の脱分極を引き起こします。複数のシナプス前入力が頻発してシナプス後膜が脱分極すると、NMDA受容体の孔を塞いでいたマグネシウムイオンが変位し、ナトリウムイオンとカルシウムイオンが神経細胞内に流入します。
 
 カルシウムイオンの流入が増えると、シグナルカスケードが始まり、細胞膜に挿入されるAMPA受容体の数が増えます。カルシウムイオンの流入が増えると、シグナルカスケードが開始され、AMPA受容体がより多く細胞膜に挿入されます。また、シグナルカスケードがグルタミン酸受容体をリン酸化することで、グルタミン酸受容体がより長く開いた状態になり、細胞内への正電荷イオンの伝導が促進されます。その結果、同じシナプス前刺激でも、より多くのグルタミン酸受容体が活性化され、より多くの正電荷イオンがシナプス後の神経細胞に入ることで、より強いシナプス後の反応を引き起こすことになります。このような増幅は、シナプスの強化または増強として知られています。 
 
 「習うより慣れろ」という言葉がありますが、これはLTPによって説明できる部分があります。練習を繰り返すたびに、神経回路のシナプス強度が強くなり、やがてタスクを正確かつ効率的に実行できるようになります。新たに強化された神経回路の結合は、シナプス前の刺激が持続すれば、数分から数週間、あるいはそれ以上持続します。
 
 <h4>LTPと病気</h4>
 
 LTPが正常に機能していれば、私たちは簡単に学習し、記憶を形成できます。しかし、LTPの異常は、アルツハイマー病、自閉症、依存症、統合失調症、多発性硬化症など、多くの神経疾患や認知障害に関与していると言われています。LTPのメカニズムが解明されれば、治療法の確立につながる可能性があります。

長期増強(LTP)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 Potentiation

synaptic strengthening in learning and memory

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 that fire together wire together. Repeated stimulation changes the types and number of ion channels in the postsynaptic membrane. Two glutamate receptors are involved: NMDA receptors and AMPA receptors.

NMDA receptors open when glutamate binds, but magnesium ions usually block the pore. At the same time, glutamate can activate AMPA receptors on the postsynaptic cell. This causes sodium ions to enter and depolarize the membrane. When many presynaptic inputs arrive in quick succession, the magnesium block is removed from the NMDA receptor. Sodium and calcium ions then enter the neuron.

The calcium influx starts a signaling cascade inside the cell. This cascade leads to more AMPA receptors being inserted into the plasma membrane. It can also phosphorylate glutamate receptors, which helps them stay open longer and lets more positively charged ions enter the cell. The same presynaptic signal then creates a stronger postsynaptic response. This increase is called synaptic strengthening, or potentiation.

LTP also helps explain why practice makes perfect. When a new task is learned, new neural circuits are reinforced by LTP. With each round of practice, the synaptic strength in those circuits becomes stronger. Over time, the task can be performed more correctly and efficiently. These strengthened connections can last from minutes to weeks or longer if presynaptic stimulation continues, so later practice can maintain the LTP.

When LTP works normally, learning and memory are easier. Problems with LTP have been linked to Alzheimer’s disease, autism, addiction, schizophrenia, and multiple sclerosis. Understanding how LTP works may help guide future therapies for these neurological and cognitive disorders.

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long-term potentiation

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...

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Explore how long-term potentiation strengthens synapses, supports learning and memory, and is linked to disorders such as Alzheimer’s disease and autism.

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Synaptic Strengthening in Learning and Memory

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