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

- [Narratore] La Long-term
depression, LTD, è un processo

di indebolimento sinattico
che si verifica nel tempo

tra le connessioni neuronali
pre e postsinaptiche.

Un meccanismo che da luogo all'LTD dipende

dalla quantità di ioni di
calcio che fluiscono nel

neurone postsinaptico dopo
la stimulazione presinaptica.

La bassa concentrazione di
calcio dovuta a una stimolazione

presinaptica infrequente può
attivare una cascata di segnali

culminanti nell'endocitosi,
o l'eliminazione

dei ricettori di glutammato
AMPA dalla membrana.

Di conseguenza, la risposta postsinaptica

alla stessa stimolazione
presinaptica sporadica

risulta ulteriormente indebolita.

Pertanto, l'LTD è importante
per l'apprendimento,

poiché le sinapsi non
utilizzate e utilizzate poco

possono indebolirsi e
addirittura essere eliminate.

Questo per liberare risorse
e spazio che possono essere

usate dal neurone per altre funzioni,

come il rafforzamento LTP
di sinapsi più importanti.

Kukushkin, Nikolay Vadimovich e Thomas James Carew. "La memoria richiede tempo". Neuron 95, n. 2 (19 luglio 2017): 259–79. [<a href="https://doi.org/10.1016/j.neuron.2017.05.029" target="__blank">Sorgente</a>]

Lüscher, Christian e Robert C. Malenka. "Potenziamento a lungo termine dipendente dal recettore NMDA e depressione a lungo termine (LTP/LTD)." Cold Spring Harbor Perspectives in Biology 4, n. 6 (1 giugno 2012): a005710. [<a href="https://doi.org/10.1101/cshperspect.a005710" target="__blank">Sorgente</a>]

long-term depression

La depressione a lungo termine, o LTD, è uno dei modi con cui la plasticità sinaptica - cambiamenti nella forza delle sinapsi chimiche- può verificarsi nel cervello. LTD è il processo di indebolimento sinaptico che si verifica nel tempo tra le connessioni neuronali pre e post-sinaptiche. L'indebolimento sinaptico del LTD funziona in opposizione al rafforzamento sinaptico da potenziamento a lungo termine (LTP) e insieme sono i principali meccanismi che sono alla base dell'apprendimento e della memoria.

<h4>Meccanismo di concentrazione degli ioni di calcio</h4>

Se nel corso del tempo, tutte le sinapsi sono rafforzate al massimo attraverso LTP o qualche altro meccanismo, il cervello raggiungere un plateau in efficienza rendendo l'apprendimento e la formazione di nuovi ricordi difficile. LTD è un modo per potare sinapsi più deboli liberando così risorse e ristabilendo la flessibilità nel sistema nervoso centrale. Un meccanismo con cui si verifica LTD dipende dal numero di ioni di calcio nel neurone post-sinaptico dopo la stimolazione presinaptica. Livelli resigui o bassi di stimolazione pressiratica portano a un basso afflusso di ioni di calcio e, di conseguenza, bassa concentrazione di ioni di calcio nel neurone post-sinaptico.

La bassa concentrazione di ioni di calcio avvia una cascata di segnalazione che culmina nell'endocitosi o la rimozione di recettori dell'acido-3-idrossico-5-metilicio-4-isoxazolepropionici (AMPA) del glutammato dalla membrana plasmatica. Di conseguenza, la risposta post-sinaptica alla stessa stimolazione presinaptica sporadica è ulteriormente indebolita, poiché ci sono meno canali per gli ioni caricati positivamente per entrare e depolarizzare la membrana. Il neurone riutilizza i recettori AMPA in un secondo momento e/o li separa nelle loro sottounità costituenti.

LTD è stato descritto per la prima volta come avvenuto nell'ippocampo, dove si pensa cancelli vecchi ricordi. Successivamente, è stato dimostrato che LTD si verifica in molte regioni del cervello come il cervelletto, lo striato e la corteccia. La presenza ubiquitaria di LTD è alla base del suo coinvolgimento nel corretto funzionamento del cervello.

<h4>LTD e malattia</h4>

Meccanismi di malfunzionamento di LTD sono pensati per contribuire a numerosi disturbi neurologici e cognitivi come la dipendenza, ritardo mentale, e il morbo di Alzheimer. La ricerca è in corso per comprendere meglio i meccanismi di LTD, come si verificano i disturbi neurologici, e per sviluppare trattamenti.

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 ...

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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

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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, 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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