Long-Term Potentiation

Long-term potentiation (LTP) occurs on any occasion where a presynaptic cell fires (once or more) at a time when the postsynaptic membrane is strongly depolarized (either through repetitive firing of the same presynaptic cell or by other means).

NMDA Channels
Most of the depolarizing current for excitatory PSP (Post-synaptic potential) is carried in the ordinary way by ligand-gated ion channels that bind glutamate. During LTP development, a second distinct subclass of channel-linked glutamate receptors - NMDA receptors (named so because they are selectively activated by the artificial glutamate analog N-methyl-D-aspartate). The NMDA-receptor channels are doubly-gated, opening only when two conditions are satisfied simultaneously:
 * 1) The membrane must be strongly depolarized (the channels are subjected to a peculiar form of voltage gating that depends on extracellular Mg2+)
 * 2) The neurotransmitter glutamate must be bound to the receptor (on the contrary, when NMDA-receptors are blocked with a specific inhibitor, LTP does not occur, even though ordinary synaptic transmission continues)

An animal treated with an NMDA inhibitor fails to learn/remember information of the type thought to depend on the hippocampus (declarative/reflexive type), but behaves almost normally otherwise.

NMDA channels, when opened, are highly permeable to Ca2+, which acts as an intracellular messenger, triggering the local changes responsible for long-term potentiation. On the contrary, LTP is prevented when Ca2+ levels are held artificially low in the postsynaptic cell (by injecting EDTA into it) and can be induced by transiently raising extracellular Ca2+ levels artificially high. The nature of the long-term changes triggered by Ca2+ is uncertain, but they are thought to involve structural alterations in the synapse.

The entry of calcium (after successful activation of NMDA-receptor channel) triggers number of events:


 * 1) Protease activation → results in cytoskeletal (morphological) changes, such as change in the shape of dendritic spines.
 * 2) Lipase activation → breakdown of fats → arachidonic acid formation → arachidonic acid exits the postsynaptic cell and bind on the presynaptic membrane → promoting even more glutamate release → thus behaving as a retrograde messenger.
 * 3) Production of second messengers:
 * 4) IP3 (inositol triphosphate):
 * 5) Stimulates release of calcium from intra-synaptosomal stores →
 * 6) Ca2+-calmodulin complex activates the Ca2+-calmodulin-depended kinase → cAMP production → cAMP activates cAMP–depended kinases by phosphorylating them → the activated kinases phosphorylate and activate transcription factors.
 * 7) Diacylglycerol (DAG) as second messengers →
 * 8) Activation of Protein Kinase C →
 * 9) Further activation of transcription factors that enable serotinin and acetylcholine-enhanced neuronal excitation associated with memory tasks.

Memory Consolidation
For memory consolidation, this process requires certain time: 5-10 minutes for minimal consolidation, 1 hour for stronger consolidation. This can occur by the rehearsal technique (as proven by psychological studies):
 * Brain has a natural tendency to rehearse newfound information
 * Rehearsal causes the mind to accelerate the process of consolidation
 * Progressively over time, more and more information is fixed in memory spaces.
 * This explains why a person can better remember in depth information on a single subject, rather than superficial information on vast amounts of different subjects.
 * This also explains why a person who is wide awake can consolidate memories better than a person who experiences mental fatigue.

Related articles

 * Learning and Memory