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

- [Verteller] Lange termijn depressie, of LTD, is een proces van synaptische verzwakking die optreedt na verloop van tijd tussen pre- en postsynaptische neuronale verbindingen. Een mechanisme waardoor LTD optreedt is afhankelijk van de hoeveelheid calciumionen die in het postsynaptische neuron stromen na presynaptische stimulatie. Een lage calciumconcentratie als gevolg van een infrequente presynaptische stimulatie kan een signaalcascade op gang brengen die uitmondt in de endocytose of verwijdering van AMPA glutamaatreceptoren uit het membraan.

Hierdoor wordt de postsynaptische respons op dezelfde sporadische presynaptische stimulatie verder verzwakt. LTD is dus belangrijk voor leren, omdat ongebruikte of zelden gebruikte synapsen worden verzwakt en zelfs kunnen worden afgekapt, waardoor middelen en ruimte vrijkomen die door de neuron kunnen worden gebruikt voor andere functies, zoals LTP versterking van belangrijkere synapsen.

langdurige depressie

Langdurige depressie, of LTD, is een van de manieren waarop synaptische plasticiteit – veranderingen in de sterkte van chemische synapsen – in de hersenen kan optreden. LTD is het proces van synaptische verzwakking dat in de loop van de tijd optreedt tussen pre- en postsynaptische neuronale verbindingen. De synaptische verzwakking van LTD werkt in tegenstelling tot synaptische versterking door langetermijnpotentiatie (LTP) en vormt samen de belangrijkste mechanismen die ten grondslag liggen aan leren en geheugen.

<h4>Calciumionenconcentratiemechanisme</h4>

Als na verloop van tijd alle synapsen maximaal worden versterkt door LTP of een ander mechanisme, zouden de hersenen in efficiëntie stagneren, waardoor leren en het vormen van nieuwe herinneringen moeilijk wordt. LTD is een manier om zwakkere synapsen te snoeien, waardoor hulpbronnen vrijkomen en de flexibiliteit terugkomt in het centrale zenuwstelsel. Eén mechanisme waardoor LTD optreedt, hangt af van het aantal calciumionen in het postsynaptische neuron na presynaptische stimulatie. Onregelmatige of lage niveaus van presynaptische stimulatie leiden tot een lage instroom van calciumionen en bijgevolg tot een lage calciumionenconcentratie in het postsynaptische neuron.

De lage calciumionconcentratie initieert een signaalcascade die culmineert in de endocytose of verwijdering van α-amino-3-hydroxy-5-methyl-4-isoxazolpropionzuur (AMPA) glutamaatreceptoren uit het plasmamembraan. Als resultaat wordt de postsynaptische respons op dezelfde sporadische presynaptische stimulatie verder verzwakt, omdat er minder kanalen zijn waar positief geladen ionen het membraan kunnen binnendringen en depolariseren. Het neuron hergebruikt de AMPA-receptoren op een later tijdstip en/of scheidt ze in hun samenstellende subeenheden.

LTD werd voor het eerst beschreven als voorkomend in de hippocampus, waar men denkt dat het oude herinneringen opruimt. Vervolgens is aangetoond dat LTD voorkomt in veel hersengebieden, zoals het cerebellum, het striatum en de cortex. De alomtegenwoordige aanwezigheid van LTD ligt ten grondslag aan het belang ervan voor een goed functioneren van de hersenen.

<h4>LTD en ziekte</h4>

Er wordt gedacht dat slecht functionerende mechanismen van LTD bijdragen aan talrijke neurologische en cognitieve stoornissen zoals verslaving, mentale retardatie en de ziekte van Alzheimer. Er wordt onderzoek gedaan om de mechanismen van LTD beter te begrijpen, hoe neurologische aandoeningen optreden en om behandelingen te ontwikkelen.

Langdurige depressie

Long-term depression, or LTD, is one of the ways by which synaptic plasticity&mdash;changes in the strength of chemical synapses&mdash;can occur in the ...

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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, 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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