Long-Term Potentiation

From WikiLectures

Definition: "Long-term potentiation (LTP) occurs on any occasion when a presynaptic cell fires (once or more) at a time when the postsynaptic membrane is strongly depolarized (either through recent repetitive firing of the same presynaptic cell or by other means)."[1]

NMDA Channels[✎ edit | edit source]

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)
NMDA receptor

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:
    1. IP3 (inositol triphosphate):
      1. Stimulates release of calcium from intra-synaptosomal stores →
      2. 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.
    2. Diacylglycerol (DAG) as second messengers →
      1. Activation of Protein Kinase C →
      2. Further activation of transcription factors that enable serotinin and acetylcholine-enhanced neuronal excitation associated with memory tasks.[2]

Memory Consolidation[✎ edit | edit source]

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.

Links[✎ edit | edit source]

Related articles[✎ edit | edit source]

References[✎ edit | edit source]

  1. ALBERTS, B – JOHNSON, A – LEWIS, J, et al. Molecular Biology of the Cell [online] 4th edition. New York : Garland Science, 2002. Available from <http://www.ncbi.nlm.nih.gov/books/NBK26910/>. ISBN 0-8153-3218-1.
  2. RANG, H. P. – DALE, M.M.. Pharmacology. 5. edition. Edinburgh : Churchill Livingstone, 2003. ISBN 0-443-07145-4. Page 187

Sources[✎ edit | edit source]

  • POKORNY, Jaroslav. Potentiation [lecture for subject Physiology, specialization General Medicine, 1st faculty of Medicine Charles University in Prague]. Prague. 2010. 

Bibliography[✎ edit | edit source]

  • HALL, John E – GUYTON, Arthur Clifton. Guyton and Hall Textbook of Medical Physiology. 11. edition. Saunders/Elsevier, 2005. ISBN 0721602401.
  • DESPOPOULOS, Agamnenon – SILBERNAGL, Stefan. Color Atlas of Physiology. 5. edition. Thieme, 2003. ISBN 3135450058.