Long-term depression ( LTD) is a phenomenon that is the opposite of long-term potentiation (LTP). In LTD, communication across the synapse is silenced. LTD plays an important role in the cerebellum, in implicit procedural memory, where the neural networks involved in erroneous movements are inhibited by the silencing of their synaptic connections. LTD is what allows us to correct our motor procedures when learning how to perform a task.
Of course, memorization does not depend solely on the LTP of a few synapses in the hippocampus. For example, several studies indicate that the major neuromodulation systems in the brain major neuromodulation systems (such as those which use dopamine or serotonin) also greatly influence synaptic plasticity.
These neuromodulators are part of the molecular mechanisms through which factors such as motivation, rewards, and emotions can influence learning. Scientists are therefore starting to be able to relate psychological observations to specific molecular processes, even though we are still far from understanding all of the influences to which the billions of connections in our brain are subjected as they are modified every day.
Even though the neurons of the hippocampus may seem like just a transit
point in the establishment of long-term memory, they actually display
a great deal of plasticity. This plasticity is manifested chiefly
through the phenomenon of long-term potentiation (LTP),
which was discovered in the hippocampus in 1973 but has subsequently
been demonstrated in many regions of the cortex.
What happens is that when the axons that make connections to the
pyramidal neurons of the hippocampus are exposed to a high-frequency
stimulus, the amplitude of the excitatory potential measured in
these neurons is increased for a long period (up to several weeks).
the neurotransmitter released into these synapses, binds
to several different sub-types of receptors on the post-synaptic
neuron. Two of these sub-types, the receptors for AMPA and
NMDA, are especially important for LTP.
The AMPA receptor is paired
with an ion channel so that when glutamate binds to this
receptor, this channel lets sodium ions enter the post-synaptic
neuron. This influx of sodium causes the post-synaptic
dendrite to become locally depolarized, and if this depolarization
reaches the critical threshold to trigger an action potential,
the nerve impulse is transmitted to the next neuron.
The NMDA receptor is also paired
with an ion channel, but this channel admits calcium ions
into the post-synaptic cell. When this cell is at resting
potential, the calcium channel is blocked by magnesium ions
(Mg2+), so that even if glutamate binds to the receptor,
calcium cannot enter the neuron. For these magnesium ions
to withdraw from the channel, the dendrite’s membrane
potential must be depolarized.
After Nicoll, Malenka and Kauer, 1988.
And that is exactly what happens during the
high-frequency stimulation that causes LTP: the post-synaptic neuron
becomes depolarized following the sustained activation of its AMPA
receptors! The magnesium then withdraws from the NMDA receptors
and allows large numbers of calcium ions to enter the cell.
This increased concentration of calcium in
the dendrite sets off several
biochemical reactions that make this synapse more efficient
for an extended period.
To let the calcium enter the cell, the NMDA
receptor must be activated by glutamate and subjected to depolarization
simultaneously. The necessity for these two simultaneous conditions
gives this receptor associative
properties. This lets it detect the coincidence of two events
and makes it the key element in long-term potentiation.
But if this receptor is blocked with a drug,
or if the gene involved in its construction is disabled, LTP cannot