คาสิโนไทย NMDAR Extinction:
The Origin of Short Term Potentiation
Memory

 

Experimentally, long-term potentiation (LTP) can be induced by several different protocols (Shipton and Paulsen, 2013, Table 1). One of them, referred to as "tetanus", applies high frequency (~100 Hz) stimulation on the presynaptic neuron for about 1 second. This leads to postsynaptic potentiation as monitored by field excitatory postsynaptic potentials (f-EPSPs). In most cases, the time course of f-EPSP consists of two phases: an initial decaying phase and a stable phase (Figure 16-1). LTP refers to the stable phase while the initial decaying phase is known as short-term potentiation (STP) (Volianskis et al., 2013; Park et al., 2013).

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Figure 16-1. The time course of potentiation as manifested by f-EPSP.
(A) Tetanic stimulation induced both STP and LTP (open circles). The antagonist D-AP5 (filled circles) blocks the induction of STP and LTP; 0.1 μM NVP (open triangles) has no effect on the induction of potentiation whereas 1 μM NVP blocks both STP and LTP (filled triangles).
(B) STP is significantly reduced after pre-incubation with 1 μM Ro 25-6981 (filled squares) whereas LTP is not affected. 10 μM Ro 25-6981 (open squares) completely abolishes LTP.
(C) 10 μM UBP145 (filled triangles) reduces STP but spares LTP.

NVP, Ro 25-6981 and UBP145 target GluN2A-, 2B- and 2D-containing NMDARs respectively. D-AP5 is a non-selective NMDAR antagonist.
[Source: คาสิโนไทยFrance et al., 2017]

The mechanism of STP is not known. Several lines of evidence suggest that it could result from the inhibition of GluN2B-containing NMDARs by the CABT complex (คาสิโนไทยChapter 12), while the GluN2A-containing NMDARs were not affected, contributing to the sustained phase of f-EPSPs (i.e., LTP).

  1. The tetanic stimulation used to induce LTP has been demonstrated to cause microtubule invasion into spines (Mitsuyama et al., 2008), which may carry CABT into spines to block GluN2B-NMDARs.
  2. STP can be separated into two pharmacologically and kinetically distinct components: STP1 and STP2. STP2 decays more slowly than STP1. Pharmacologically, STP1 is similar to LTP, but STP2 can be abolished by Ro 25-6981, which selectively inhibits GluN2B-NMDARs (คาสิโนไทยVolianskis et al., 2013; Park et al., 2013).
  3. Tetanic stimulation is known to cause spine enlargement as early as 2 minutes (Bosch and Hayashi, 2012), in line with the finding that overexpression of CRMP2 results in an increase of mushroom-shape spines (Zhang et al., 2018).
  4. Microtubule invasion into spines takes minutes (Hu et al., 2008). This time course is approximately the same as STP.
  5. Activation of protein kinase A (PKA) requires binding of cyclic AMP (cAMP). Phosphodiesterase is an enzyme capable of degrading cAMP. Thus, its inhibitor, 3-isobutyl-1-methylxanthine (IBMX), should increase the cAMP level, thereby enhancing PKA activity (คาสิโนไทย). In agreement with the hypothesis that STP arises from CABT-GluN2B binding, IBMX has been shown to abolish STP (Schulz and Fitzgibbons, 1997).

 

Author: Frank Lee
First Published: November, 2017
Last updated: June, 2018