2-Minute Neuroscience: Long-Term Depression (LTD)

Long-term depression, or LTD, is a process by which synaptic connections between neurons are weakened. Although the functions of LTD are not completely understood, it may be important to memory formation---perhaps by resetting previous synaptic changes to allow for new memories to be formed via long-term potentiation (LTP). In this video, I discuss the best understood mechanism underlying LTD, which involves AMPA and NMDA glutamate receptors.

TRANSCRIPT:

Welcome to 2 minute neuroscience, where I simplistically explain neuroscience topics in 2 minutes or less. In this installment I will discuss long-term depression, or LTD.

LTD is a process by which synaptic connections between neurons become weaker. It is the opposing process to long-term potentiation. Although the functions of LTD are not completely understood, it’s thought to be important to memory formation, perhaps by resetting previous synaptic changes to allow for new memories to be formed via long-term potentiation.

There are several different mechanisms by which LTD may occur, but the best understood of them involves the same glutamate receptors involved in long-term potentiation: NMDA and AMPA receptors. NMDA receptors are typically blocked by a magnesium ion, which is only removed if the postsynaptic neuron becomes sufficiently depolarized as can occur through activation of the AMPA receptor; when the block is removed, calcium is able to flow into the neuron, causing further depolarization. While long-term potentiation typically occurs after brief but high-intensity stimulation of a post-synaptic neuron, LTD can be caused by prolonged low-intensity stimulation or stimulation that occurs after the firing of an action potential. With the type of modest stimulation that results in LTD, there is not enough depolarization to cause widespread removal of the magnesium blockage of the NMDA receptor. However, there is enough to cause some NMDA receptors to allow calcium into the cell. This low level of calcium is insufficient to activate the enzymes that facilitate long-term potentiation, but it is thought to activate a cellular cascade that causes the removal of AMPA receptors. This reduces the number of glutamate receptors on the postsynaptic neuron and weakens the synapse.

LTD may also result in other changes that decrease the strength of synapses, like a decrease in the amount of glutamate released from the presynaptic neuron, and it also can involve other receptors like metabotropic glutamate receptors or other neurotransmitter receptors altogether.

REFERENCE:

Kandel ER, Schwartz JH, Jessell TM 2000. Principles of Neural Science, 5th ed. McGraw-Hill, New York.

[LA-cmuo]

Thanks, this video cured my long-term depression

[cait]

These videos are a godsend. Been trying to learn this for 6 hours and in 4 minutes I completely understand LTP AND LTD. thank you.

[oldworldglam]

Two minute neuroscience is my new teacher.

[aMotionless]

I clicked on the wrong video.. I dont understand anything that is being said. But it was interesting enough to watch the whole video.

[richymt]

This two minute video explains better than my 20 minute lecture on the topic

[haroldpinteresque]

Wish he'd add 27 seconds and do a "so what" -- I get the details, but how does this roll up to the bigger picture?

[bisoffi]

Great video, simple and straight to the point! thank you

[aldobayliss]

hello in summary to be able to reverse or reduce this damage in the communication of these neurotransmitter networks, is it ideal to supplement with glutamate, calcium and magnesium before resorting to drugs such as prozac? thanks

[at_]

Why doesn't the influx of calcium activate the removal of ampa receptors during long term potentiation?

[aatiqaaamir]

Can you give some example from real life ?

[elleflock]

Can anyone think of a real life example of how this would occur? I'm struggling to conceptualize the type of situation which would involve slow, sustained, low intensity activation of a synaptic pathway!

[Alexx]

Great video, but sounds like you're saying simulation instead of stimulation. IDK if that's just me.