Name: how synapses strengthen during learning
Uploaded: 2023-04-30T10:12:15.000Z
Duration: 1 min 25 s
Channel: JoVE

Long-term potentiation, or LTP, is a process of synaptic strengthening that occurs over time between pre and post synaptic neuronal connections.
In one mechanism, when presynaptic neurons repeatedly fire and stimulate the postsynaptic cell, this action induces changes in the type and number of ion channels in the post synaptic membrane such as one class of glutamate receptors called N-methyl-D-aspartate, or NMDA.
NMDA receptors are usually inactivated by magnesium ions, however, with strong depolarization from repeated stimulation, the magnesium ions are displaced allowing calcium ions to enter.
This calcium influx initiates a signaling cascade that culminates in a second class of glutamate receptors. Alpha amino three hydroxy five methyl four isoxazolepropionic acid, or AMPA for short, inserting into the membrane. In this case, more positive ions flow into the neuron making a stronger postsynaptic response to the same presynaptic stimulation.
LTP is essential for learning, and is one way to explain the adage practice makes perfect since the newly strengthened response can last from minutes to weeks or longer if the presynaptic stimulation persists.

long-term potentiation

Long-term Potentiation

Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity&#8212;changes in the strength of chemical synapses&#8212;can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Hebbian LTP
LTP can occur when presynaptic neurons repeatedly fire and stimulate the postsynaptic neuron. This is called Hebbian LTP since it follows from Donald Hebb&#39;s 1949 postulate that &#34;neurons that fire together wire together.&#34; The repeated stimulation from presynaptic neurons induces changes in the type and number of ion channels in the postsynaptic membrane.
Two types of postsynaptic receptors of the excitatory neurotransmitter glutamate are involved in LTP: 1)N-methyl-D-aspartate or NMDA receptors and 2) &#945;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or AMPA receptors. Although NMDA receptors open upon glutamate binding, their pore is usually blocked by magnesium ions that prevent other positively charged ions from entering the neuron. However, glutamate released from presynaptic neurons can bind to postsynaptic AMPA receptors, causing an influx of sodium ions that results in membrane depolarization. When the postsynaptic membrane is depolarized by multiple frequent presynaptic inputs, the magnesium ion blocking the NMDA receptor pore is displaced, allowing sodium and calcium ions to flow into the neuron.
The increased calcium ion influx then initiates a signaling cascade that culminates in more AMPA receptors being inserted into the plasma membrane. Alternatively, the signaling cascade may phosphorylate glutamate receptors&#8212;enabling them to stay open for a longer duration and enhancing the conductance of positively charged ions into the cell. As a result, the same presynaptic stimulation will now evoke a stronger postsynaptic response given that more glutamate receptors will be activated and more positively charged ions will enter the postsynaptic neuron. The amplification that occurs is known as synaptic strengthening or potentiation.
The adage &#34;practice makes perfect&#34; can be partly explained by LTP. When a novel task is being learned, new neural circuits are reinforced using LTP. After each iteration of practice, the synaptic strength in the neural circuits becomes stronger, and soon the task can be performed correctly and efficiently. The newly strengthened connections can last from minutes to weeks or longer if the presynaptic stimulation persists, meaning that each subsequent time the task is performed, the LTP is maintained.
LTP and Disease
When LTP functions normally, we can learn and form memories with ease. However, abnormalities in LTP have been implicated in many neurological and cognitive disorders such as Alzheimer&#39;s disease, autism, addiction, schizophrenia, and multiple sclerosis. A better understanding of the mechanisms behind LTP could eventually lead to therapies.

Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity&#8212;changes in the strength of chemical synapses&#8212;can occur in the ...

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Channels and the Electrical Properties of Membranes

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KEY TERMS AND CONCEPTS

how synapses strengthen during learning

Long-term potentiation, or LTP, is a way the brain strengthens synapses over time. A synapse is the chemical connection between neurons. LTP is one form of synaptic plasticity, which means changes in synapse strength. It works opposite to 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 repeatedly fires and stimulates a postsynaptic neuron. This is called Hebbian LTP. It follows Donald Hebb's idea that neurons that fire together wire together. Repeated stimulation changes the type and number of ion channels in the postsynaptic membrane.

Two glutamate receptors are important in this process: NMDA receptors and AMPA receptors. NMDA stands for N-methyl-D-aspartate, and AMPA stands for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid. Glutamate is an excitatory neurotransmitter. NMDA receptors open when glutamate binds, but magnesium ions usually block the pore. Glutamate can also bind to AMPA receptors, which lets sodium enter the neuron and depolarize the membrane.

When the postsynaptic membrane is depolarized by repeated input, the magnesium block on the NMDA receptor is removed. This lets sodium and calcium ions flow into the neuron. The rise in calcium starts a signaling cascade. That cascade can add more AMPA receptors to the plasma membrane. It can also phosphorylate glutamate receptors so they stay open longer and allow more positive ions to enter. The same presynaptic signal then produces a stronger postsynaptic response. This increase is called synaptic strengthening, or potentiation.

LTP also helps explain why practice improves performance. When a person learns a new task, new neural circuits are reinforced through LTP. With each round of practice, the synaptic strength in those circuits grows stronger. The result is better and faster performance. These strengthened connections can last from minutes to weeks or longer if the presynaptic stimulation continues.

When LTP works normally, learning and memory are easier. Problems with LTP have been linked to several neurological and cognitive disorders, including Alzheimer's disease, autism, addiction, schizophrenia, and multiple sclerosis. A better understanding of LTP may help lead to future therapies.

How Synapses Strengthen During Learning

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the-role-of-ion-channels-in-neuronal-computation

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Long-term potentiation, or LTP, is a way the brain strengthens synapses over time. A synapse is the chemical connection between neurons. LTP is one form of synaptic plasticity, which means changes in synapse strength. It works opposite to 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 repeatedly fires and stimulates a postsynaptic neuron. This is called Hebbian LTP. It follows...

long-term depression

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Long-term depression, or LTD, is a form of synaptic weakening in the brain. It is one way synaptic plasticity, or changes in the strength of chemical synapses, can occur over time between presynaptic and postsynaptic neurons. LTD works opposite long-term potentiation, or LTP, which strengthens synapses. Together, LTD and LTP help support learning and memory. LTD also helps keep the brain flexible. If synapses stayed maximally strengthened for too long, the brain would become less efficient and...

key terms and concepts

Explore how long-term potentiation strengthens synapses, helps learning and memory, and involves NMDA and AMPA receptors in the brain.

How Synapses Strengthen During Learning | JoVE K12

cell biology

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How Synapses Strengthen During Learning

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