Experimentally, long-term potentiation (LTP) can be induced by several different protocols
(คาสิโนไทยShipton 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).
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: France 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
(Chapter 12), while the GluN2A-containing NMDARs were not affected, contributing to the sustained phase of f-EPSPs (i.e., LTP).
- 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.
- 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
(Volianskis et al., 2013;
Park et al., 2013).
- 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).
- Microtubule invasion into spines takes minutes (Hu et al., 2008).
This time course is approximately the same as STP.
- 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
In agreement with the hypothesis that STP arises from CABT-GluN2B binding, IBMX has been shown to abolish STP
(คาสิโนไทยSchulz and Fitzgibbons, 1997).
Author: Frank Lee
First Published: November, 2017
Last updated: June, 2018