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

Depressão de longo prazo ou LTD é um processo de enfraquecimento sináptico que ocorre ao longo do tempo entre conexões neuronais pré e pós-sinápticas. Um mecanismo pelo qual o LTD ocorre depende da quantidade de íons de cálcio fluindo para o neurônio pós-sináptico após a estimulação pré-sináptica. A baixa concentração de cálcio devido à estimulação pré-sináptica infrequente pode iniciar uma cascata de sinalização que culmina na endocitose ou remoção dos recetores de glutamato AMPA da membrana.Como resultado, a resposta pós-sináptica para a mesma estimulação pré-sináptica esporádica é ainda mais enfraquecida. Assim, a LTD é importante para a aprendizagem, uma vez que sinapses não utilizadas ou raramente utilizadas estão enfraquecidos e podem até ser podadas, liberando recursos e espaço que podem ser usados pelo neurônio para outras funções, como o fortalecimento LTP de sinapses mais importantes.

Kukushkin, Nikolay Vadimovich e Thomas James Carew. "A memória leva tempo." Neuron 95, nº 2 (19 de julho de 2017): 259–79. [<a href="https://doi.org/10.1016/j.neuron.2017.05.029" target="__blank">Fonte</a>]

Lüscher, Christian e Robert C. Malenka. "Potenciação de longo prazo dependente do receptor NMDA e depressão de longo prazo (LTP / LTD)." Cold Spring Harbor Perspectives in Biology 4, nº 6 (1º de junho de 2012): a005710. [<a href="https://doi.org/10.1101/cshperspect.a005710" target="__blank">Fonte</a>]

depressão a longo prazo

A depressão a longo prazo, ou LTD, é uma das maneiras pelas quais a plasticidade sináptica—alteração na força das sinapses químicas—pode ocorrer no cérebro. LTD é o processo de enfraquecimento sináptico que ocorre ao longo do tempo entre conexões neuronais pré e pós-sinápticas. O enfraquecimento sináptico da LTD funciona em oposição ao fortalecimento sináptico por uma potencialização de longo prazo (LTP) e juntos são os principais mecanismos que servem de base para a aprendizagem e memória.
 
 <h4>Mecanismo de Concentração de Iões de Cálcio</h4>
 
 Se com o tempo, todas as sinapses forem maximamente fortalecidas através da LTP ou de algum outro mecanismo, o cérebro iria atingir um limite de eficiência, dificultando a aprendizagem e a formação de novas memórias. LTD é uma maneira de podar sinapses mais fracas, libertando recursos e dando novamente flexibilidade ao sistema nervoso central. Um mecanismo pelo qual a LTD ocorre depende do número de iões de cálcio no neurónio pós-sináptico após a estimulação pré-sináptica. Níveis pouco frequentes ou baixos de estimulação pré-sináptica levam ao baixo influxo de iões de cálcio e, consequentemente, baixa a concentração de iões de cálcio no neurónio pós-sináptico.
 
 A baixa concentração de iões de cálcio inicia uma cascata de sinalização que culmina na endocitose ou remoção de receptores de glutamato de ácido α-amino-3-hidroxi-5-metil-4-isoxazolepropiónico (AMPA) da membrana plasmática. Como resultado, a resposta pós-sináptica à mesma estimulação pré-sináptica esporádica é ainda mais enfraquecida, uma vez que há menos canais para iões carregados positivamente entrarem e despolarizarem a membrana. O neurónio reutiliza posteriormente os receptores AMPA e/ou separa-os nas suas subunidades constituintes.
 
 A LTD foi descrita pela primeira vez como ocorrendo no hipocampo, onde se pensa que limpa memórias antigas. Posteriormente, tem sido mostrado que a LTD ocorre em muitas regiões cerebrais, como o cerebelo, o estriado e o córtex. A presença ubíqua da LTD está por trás da sua importância no bom funcionamento cerebral.
 
 <h4>LTD e Doenças</h4>
 
 Acredita-se que mecanismos defeituosos da LTD contribuam para numerosos distúrbios neurológicos e cognitivos, como vício, atraso mental e doença de Alzheimer. Investigações estão em curso para entender melhor os mecanismos da LTD, como ocorrem os distúrbios neurológicos e desenvolver tratamentos.

Depressão a Longo Prazo

A depressão de longo prazo, ou LTD, é uma das maneiras pelas quais a plasticidade sináptica - mudanças na força das sinapses químicas - pode ocorrer no ...

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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

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...

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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key terms and concepts

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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