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

Potenciação a longo prazo, ou LTP, é um processo de enfraquecimento sináptico que ocorre ao longo do tempo entre conexões neuronais pré e pós-sinápticas. Em um mecanismo, quando os neurônios pré-sinápticos disparam repetidamente e estimulam a célula pós-sináptica, esta ação induz mudanças no tipo e número de canais iónicos na membrana pós-sináptica, como uma classe de recetores de glutamato denominados N-metil-D-aspartato ou NMDA. Os recetores NMDA são geralmente inativados por iões de magnésio.No entanto, com a forte despolarização da estimulação repetida, os iões de magnésio são deslocados, permitindo a entrada de iões de cálcio. Este influxo de cálcio inicia uma cascata de sinalização que culmina em uma segunda classe de recetores de glutamato, ácido alfa-amino-3-hidroxi-5-metil-4-isoxazolpropiônico, AMPA para abreviar, seja inserido na membrana. Neste caso, iões mais positivos fluem para o neurónio, fazendo uma forte resposta pós-sináptica à mesma estimulação pré-sináptica.O LTP é essencial para o aprendizado, e é uma maneira para explicar o ditado de que a prática leva à perfeição já que a resposta recentemente reforçada pode durar de minutos a semanas ou mais se a estimulação pré-sináptica persistir.

Nicoll, Roger A. "Uma breve história da potenciação de longo prazo." Neuron 93, nº 2 (18 de janeiro de 2017): 281–90. [<a href="https://doi.org/10.1016/j.neuron.2016.12.015" target="__blank">Fonte</a>]

Bliss, T. V. P., G. L. Collingridge e R. G. M. Morris. "Plasticidade sináptica na saúde e na doença: introdução e visão geral." Transações Filosóficas da Royal Society B: Ciências Biológicas 369, nº 1633 (5 de janeiro de 2014). [<a href="https://doi.org/10.1098/rstb.2013.0129" target="__blank">Fonte</a>]

potenciação a longo prazo

A potenciação a longo prazo, ou LTP, é uma das maneiras pelas quais a plasticidade sináptica—alterações na força das sinapses químicas—pode ocorrer no cérebro. LTP é o processo de fortalecimento sináptico que ocorre ao longo do tempo entre conexões neuronais pré e pós-sinápticas. O fortalecimento sináptico da LTP funciona em oposição ao enfraquecimento sináptico da depressão de longo prazo (LTD) e, em conjunto, são os principais mecanismos que servem de base para a aprendizagem e memória.
 
 <h4>LTP Hebbiano</h4>
 
 A LTP pode ocorrer quando neurónios pré-sinápticos disparam repetidamente e estimulam o neurónio pós-sináptico. Isso tem o nome de LTP Hebbiano, uma vez que segue o postulado de Donald Hebb em 1949 de que “neurónios que disparam juntos conectam-se entre si”. A estimulação repetida dos neurónios pré-sinápticos induz alterações no tipo e número de canais iónicos na membrana pós-sináptica.
 
 Dois tipos de receptores pós-sinápticos do neurotransmissor excitatório glutamato estão envolvidos na LTP: 1) receptores N-metil-D-aspartato ou NMDA e 2) receptores de ácido α-amino-3-hidroxi-5-metil-4-isoxazolepropiónico ou AMPA. Embora os receptores NMDA abram com a ligação do glutamato, os seus poros estão geralmente bloqueados por iões de magnésio que impedem outros iões carregados positivamente de entrarem no neurónio. No entanto, o glutamato libertado de neurónios pré-sinápticos pode ligar-se a receptores AMPA pós-sinápticos, causando um influxo de iões de sódio que resulta em despolarização da membrana. Quando a membrana pós-sináptica é despolarizada por múltiplos sinais pré-sinápticos frequentes, o ião de magnésio que bloqueia o poro do receptor NMDA desprende-se, permitindo que iões de sódio e cálcio fluam para dentro do neurónio.
 
 O aumento do fluxo de iões de cálcio inicia então uma cascata de sinalização que culmina em mais receptores AMPA a serem inseridos na membrana plasmática. Alternativamente, a cascata de sinalização pode fosforilar receptores de glutamato—permitindo que eles permaneçam abertos por mais tempo e aumentando a condutividade de iões carregados positivamente para a célula. Como resultado, a mesma estimulação pré-sináptica agora evocará uma resposta pós-sináptica mais forte, dado que mais receptores de glutamato serão ativados e mais iões carregados positivamente irão entrar no neurónio pós-sináptico. A amplificação que ocorre é conhecida como fortalecimento sináptico ou potencialização.
 
 O ditado “a prática faz a perfeição” pode ser parcialmente explicado pela LTP. Quando uma nova tarefa está a ser aprendida, novos circuitos neurais são reforçados usando a LTP. Após cada iteração da prática, a força sináptica nos circuitos neurais torna-se mais forte, e em breve a tarefa pode ser executada de forma correta e eficiente. As conexões recém-reforçadas podem durar de minutos a semanas ou mais se a estimulação pré-sináptica persistir, o que significa que de cada vez que a tarefa é executada a LTP é mantida.
 
 <h4>LTP e Doenças</h4>
 
 Quando a LTP funciona normalmente, podemos aprender e formar memórias com facilidade. No entanto, anormalidades na LTP têm sido implicadas em muitas doenças neurológicas e cognitivas, como doença de Alzheimer, autismo, vício, esquizofrenia e esclerose múltipla. Uma melhor compreensão dos mecanismos por trás da LTP poderá eventualmente levar a terapias.

Potenciação a Longo Prazo

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

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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.

Synaptic Strengthening in Learning and Memory

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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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Synaptic Strengthening in Learning and Memory

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