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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
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
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.