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

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.

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