Long-term depression

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Under long-term depression (eng: long-term depression, LTD ) is defined as a permanent weakening of the signal transmission at the synapses of nerve cells. Together with its counterpart - long-term potentiation (LTP), LTD represents one of the cellular foundations of learning and memory. It is now commonly assumed that information is permanently stored in nervous systems through these forms of synaptic plasticity . Although it has not yet been possible to attribute learning directly to LTP and LTD, there are a number of indirect indications that they represent the cellular mechanism of certain forms of learning.

LTD in the brain

LTD was measured in different brain regions, including the cerebral cortex (visual cortex, prefrontal cortex), the amygdala, as well as the hippocampus and the cerebellum . Different forms of LTD occur in the different areas, each of which uses different molecular mechanisms.

LTD in the spinal cord

The presence of an LTD was also demonstrated in animal experiments and in healthy volunteers in the spinal cord, especially in the nociceptive system. The European Pain Prize was awarded in 2005 for the findings regarding the modulability of pain processing by the LTD and efforts are being made to make corresponding methods usable in pain therapy.

Electrophysiology

Like other forms of synaptic plasticity, LTD can only be measured in response to artificial electrical stimulation. Axons of nerve cells are stimulated with a thin electrode and the synaptic response of cells that form synapses with these axons is measured with another electrode. LTD can be triggered by different stimulations. A frequently used stimulation pattern is, for example, the so-called low frequency stimulation , in which nerve cells are stimulated with a frequency of 1 Hz for 15 minutes. With this irritation, LTD can be reliably induced in the hippocampus. Most experiments on synaptic plasticity are done on thin sections of nerve tissue, but it is also possible to study LTD in the intact brain.

Molecular and Cellular Mechanisms

LTD in the hippocampus

Two forms of LTD are known in the hippocampus: so-called NMDA-receptor-dependent LTD (NMDAR-LTD) and metabotropic glutamate-receptor-dependent LTD (mGluR-LTD). With NMDAR-LTD, the so-called NMDA receptor is activated by a simultaneous release of a transmitter at the synapse and an electrical excitation, so that calcium can flow into the cell. As an intracellular signaling molecule, calcium also activates a number of other enzymes in LTD, which regulate the signal transmission at the synapse. With mGluR-LTD, metabotropic glutamate receptors are activated, which, as so-called G proteins, trigger the release of calcium from intracellular stores via additional signaling molecules. Both types of LTD can occur at the same synapses, but use separate mechanisms. It is not yet known to what extent they influence each other or actually run completely independently of each other.

LTD and learning

For a long time, LTD was only seen as the reverse process of the long-term potentiation of LTP. In the meantime, however, we know that LTD represents its own form of synaptic plasticity, without which learning and memory would not be possible. For example, mice do not learn to orient themselves spatially if the LTD is artificially blocked.

Individual evidence

  1. ↑ Jürgen Sandkühler: Translating synaptic plasticity into sensation . In: Brain . tape 138 , no. 9 , September 1, 2015, ISSN  0006-8950 , p. 2463–2464 , doi : 10.1093 / brain / awv193 ( oup.com [accessed June 20, 2017]).
  2. ↑ Martin Mücke, Henning Cuhls, Lukas Radbruch, Tobias Weigl, Roman Rolke: Evidence of Heterosynaptic LTD in the Human Nociceptive System: Superficial Skin Neuromodulation Using a Matrix Electrode Reduces Deep Pain Sensitivity . In: PLOS ONE . tape 9 , no. 9 , September 17, 2014, ISSN  1932-6203 , p. e107718 , doi : 10.1371 / journal.pone.0107718 , PMID 25229556 , PMC 4168234 (free full text) - ( plos.org [accessed June 20, 2017]).
  3. ↑ K. Jung, D. Lelic, S. Rottmann, Am Drewes, L. Petrini: Electrical low-frequency stimulation induces central neuroplastic changes of pain processing in man . In: European Journal of Pain . tape 16 , no. 4 , April 1, 2012, ISSN  1532-2149 , p. 509-521 , doi : 10.1016 / j.ejpain.2011.08.006 ( wiley.com [accessed June 20, 2017]).
  4. ↑ Neurostimulation should erase the "pain memory": European pain award to Aachen researchers. Retrieved June 20, 2017 .
  5. ↑ Studies | Bomedus ... and the pain is forgotten. Retrieved June 20, 2017 .
  6. ↑ VY Bolshakov, SA Siegelbaum: ???. in: Science . Washington 1994, 264, p. 1148. ISSN  0036-8075
  7. ↑ M. Migaud et al. a .: Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein in: Nature . London 1998,396, p. 433. ISSN  0028-0836

literature

  • ER Kandel, JH Schwartz, TM Jessell : Neurosciences. An introduction. Spectrum Akad. Verl., Heidelberg 1996. ISBN 3-86025-391-3
  • RF Thompson: The Brain. From the nerve cell to behavior control. Spectrum Akad. Verl., Heidelberg 2001. ISBN 3-8274-1080-0
  • J. Dudel, R. Menzel, RF Schmidt: Neuroscience. From molecule to cognition. Springer, Berlin 2001. ISBN 3-540-41335-9

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