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

- [내레이터]] 장기저하 혹은 LTD는시간이 지나면서 발생하는 시냅스 앞과 후면의뉴런의 연결 간 시냅스의 약화 과정입니다.LTD를 발생시키는 하나의 메커니즘은시냅스 전 자극 후 시냅스 후 뉴런으로흘러드는 칼슘이온의 양에 좌우됩니다.드물게 발생하는 시냅스 전 자극으로 인한 낮은칼슝이온의 농도는 엔도시토시스에서 정점에달하는 시그널링 케스케이드 혹은 세포막에서의 AMPA글루타메이트 수용체 제거를 유발할 수 있습니다.그 결과로 동일한 산발적 시냅스 전 자극에대한 시냅스 후부의 반응은 더욱 약해지게됩니다.따라서 사용되지 않거나 드물게 사용되는시냅스는 약해지고 심지어 제거될 수도 있기에LTD에는 학습이 중요합니다.LTP와 같은 다른 기능을 위해 뉴런이 사용할 수있는 자원과 공간의 확보는 더욱 중요한 시냅스를강화시켜줍니다.

쿠쿠쉬킨, 니콜라이 바디모비치, 토마스 제임스 카레우. "기억에는 시간이 걸린다." Neuron 95, no. 2 (2017년 7월 19일): 259–79. [<a href="https://doi.org/10.1016/j.neuron.2017.05.029" target="__blank">소스</a>]

뤼셔, 크리스티안, 로버트 C. 말렌카. "NMDA 수용체 의존성 장기 강화 및 장기 우울증(LTP/LTD)." Cold Spring Harbor Perspectives in Biology 4, no. 6 (2012년 6월 1일): a005710. [<a href="https://doi.org/10.1101/cshperspect.a005710" target="__blank">소스</a>]

장기저하

장기저하(long-term depression, 줄여서 LTD; 장기 억압 작용)는 시냅스 가소성(synaptic plasticity; 화학 시냅스의 강도 변화)이 뇌에서 발생할 수 있는 방법의 하나입니다. LTD는 시냅스 전후의 신경 연결 사이에 시간이 지남에 따라 발생하는 시냅스 약화 과정입니다. LTD의 시냅스 약화는 장기강화(long-term potentiation, 줄여서 LTP; 장기 상승 작용)에 의한 시냅스 강화와는 반대로 작용하며, 함께 학습과 기억의 기초가 되는 주요 기작입니다.
 
 <h4>칼슘 이온 농도 기작</h4>
 
 시간이 지남에 따라 모든 시냅스가 LTP 또는 다른 기작을 통해 최대한 강화되면, 학습과 새로운 기억의 형성이 어려워집니다. LTD는 약한 시냅스를 정리하는 방법이며, 이를 통해 자원을 확보하고 중추신경계의 유연성을 다시 살리는 방법입니다. LTD가 발생하는 기작 중 하나는 시냅스전(presynaptic) 자극 후 시냅스이후 뉴런(postsynaptic neuron)의 칼슘 이온 수에 달려 있습니다. 시냅스전 자극의 빈도가 낮으면 칼슘 이온 유입이 적고 결과적으로 시냅스이후 뉴런의 칼슘 이온 농도가 낮아집니다.
 
 낮은 칼슘 이온 농도는 원형질막(plasma membrane)에서 AMPA 글루탐산(glutamate; 글루타메이트) 수용체(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, 줄여서 AMPA receptor)를 내포작용(endocytosis)을 통해 제거하는 신호의 연쇄반응(signaling cascade)을 시작합니다. 결과적으로, 전과 동일하게 산발적으로 발화되는 시냅스전 자극에 대한 시냅스 후 반응은 양전하 이온이 막에 들어가고 탈분극(depolarization)하는 채널이 적어져 더 약화됩니다. 뉴런은 이렇게 모은 AMPA 수용체를 재사용하거나 단위체(subunit)로 분해합니다.
 
 LTD는 처음 해마(hippocampus)에서 발생하는 것으로 묘사되었으며, 이곳에서 오래된 기억을 지우는 것으로 간주했습니다. 그 후, LTD는 소뇌(cerebellum), 선조체(striatum), 겉질(cortex; 피질)과 같은 다양한 뇌 영역에서 발생하는 것으로 나타났습니다. LTD의 흔한 존재는 적절한 뇌 기능에 있어 그 중요성을 강조합니다.
 
 <h4>LTD와 질병</h4>
 
 LTD의 오작동 기작은 중독, 지적 장애, 알츠하이머병과 같은 수많은 신경인지장애에 기여하는 것으로 간주합니다. LTD의 기작, 신경장애가 발생하는 과정, 그리고 이에 대한 치료법을 개발하기 위한 연구가 진행 중입니다.

장기 우울증 (LTD)은 시냅스 가소성 (화학적 시냅스의 강도 변화)이 발생할 수있는 방법 중 하나입니다.

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주요 용어 및 개념

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

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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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