Name: synaptic weakening in memory circuits
Uploaded: 2023-04-30T10:12:23.000Z
Duration: 1 min 3 s
Channel: JoVE

Long-term depression, or LTD, is a process of synaptic weakening that occurs over time between pre- and postsynaptic neuronal connections.
One mechanism by which LTD occurs is dependent on the amount of calcium ions flowing into the postsynaptic neuron after presynaptic stimulation. Low calcium concentration due to infrequent presynaptic stimulation can initiate a signaling cascade that culminates in the endocytosis or removal of AMPA glutamate receptors from the membrane. As a result, the postsynaptic response to the same sporadic presynaptic stimulation is further weakened.
Thus, LTD is important for learning, since unused or rarely used synapses are weakened and can even be pruned away, freeing up resources and space that can be used by the neuron for other functions, such as LTP strengthening of more important synapses.&#160;

long-term depression

Long-term Depression

Long-term depression, or LTD, is one of the ways by which synaptic plasticity&#8212;changes in the strength of chemical synapses&#8212;can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over time, all synapses are maximally strengthened through LTP or some other mechanism, the brain would plateau in efficiency, making learning and forming new memories difficult. LTD is a way to prune weaker synapses thereby freeing up resources and putting flexibility back into the central nervous system. One mechanism by which LTD occurs depends on the number of calcium ions in the postsynaptic neuron after presynaptic stimulation. Infrequent or low levels of presynaptic stimulation lead to low calcium ion influx and consequently, low calcium ion concentration in the postsynaptic neuron.
The low calcium ion concentration initiates a signaling cascade that culminates in the endocytosis or removal of &#945;-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors from the plasma membrane. As a result, the postsynaptic response to the same sporadic presynaptic stimulation is further weakened, since there are fewer channels for positively charged ions to enter and depolarize the membrane. The neuron reuses the AMPA receptors at a later time and/or separates them into their constituent subunits.
LTD was first described as occurring in the hippocampus, where it is thought to clear old memories. Subsequently, LTD has been shown to occur in many brain regions such as the cerebellum, striatum, and cortex. The ubiquitous presence of LTD underlies its importance in proper brain functioning.
LTD and Disease
Malfunctioning mechanisms of LTD are thought to contribute to numerous neurological and cognitive disorders such as addiction, mental retardation, and Alzheimer&#39;s disease. Research is ongoing to better understand the mechanisms of LTD, how neurological disorders occur, and to develop treatments.

Long-term depression, or LTD, 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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Cell Biology

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Channels and the Electrical Properties of Membranes

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KEY TERMS AND CONCEPTS

synaptic weakening in memory circuits

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 learning new information would be harder. By pruning weaker synapses, LTD frees up resources in the central nervous system. This balance helps neural circuits keep working properly.

One common LTD mechanism depends on calcium ion concentration in the postsynaptic neuron. When presynaptic stimulation is infrequent or weak, less calcium enters the postsynaptic cell. That low calcium level starts a signaling pathway that removes AMPA glutamate receptors from the plasma membrane by endocytosis, or receptor uptake into the cell. With fewer AMPA receptors, the same presynaptic signal produces a weaker postsynaptic response because fewer positive ions can enter to depolarize the membrane.

The neuron can reuse AMPA receptors later, or it can separate them into smaller parts. 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 may contribute to addiction, mental retardation, and Alzheimer’s disease, and researchers continue to study these links.

Synaptic Weakening in Memory Circuits

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long-term potentiation

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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, 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 depression weakens synapses, balances long-term potentiation, and supports learning, memory, and brain flexibility in the brain.

Synaptic Weakening in Memory Circuits | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

Synaptic Weakening in Memory Circuits

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