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Review
. 2008 Dec;14(6):598-608.
doi: 10.1177/1073858408320643. Epub 2008 Oct 20.

Dissecting the components of long-term potentiation

Jay A Blundon  1 , Stanislav S Zakharenko
Affiliations
Review

Dissecting the components of long-term potentiation

Jay A Blundon et al. Neuroscientist. 2008 Dec.

Abstract

The formation of memories relies in part on plastic changes at synapses between neurons. Although the mechanisms of synaptic plasticity have been studied extensively over several decades, many aspects of this process remain controversial. The cellular locus of expression of long-term potentiation (LTP), a major form of synaptic plasticity, is one of the most important unresolved phenomena. In this article, some recent advances in this area made possible by the development of new imaging tools are summarized. These studies have demonstrated that LTP is compound in nature and consists of both presynaptic and postsynaptic components. Some features of presynaptic and postsynaptic changes during compound LTP are also reviewed.

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Figures

Figure 1
Figure 1. The FM 1-43 assay is a direct and reliable indicator of presynaptic activity in hippocampal slices
A. The presynaptic terminal is loaded with the FM 1-43 dye (red dots) through endocytosis. The dye is then unloaded with neurotransmitter (blue) from synaptic vesicles via exocytosis. B. Fluorescent images of presynaptic boutons loaded with FM 1-43 in hippocampal slices. FM 1-43 was unloaded during synaptic stimulation starting at 0'00”. C. The rate of FM 1-43 unloading is positively associated with”] the frequency of synaptic stimulation.
Figure 2
Figure 2. Dissecting postsynaptic LTP from compound LTP
A. The FM 1-43 assay was used to dissect LTP induced at CA3-CA1 synapses with the 200-Hz (red) or 50-Hz (green) stimulation protocols. The arrow depicts the onset of LTP induction. B. Presynaptic function assayed as rate of FM 1-43 unloading in response to 1.5 Hz synaptic stimulation (bar) was enhanced during the 200-Hz LTP (red triangles) but not during the 50-Hz LTP (green squares) compared to that before LTP was induced (black circles).
Figure 3
Figure 3. The synaptopHluorin assay directly and continuously monitors presynaptic activity in hippocampal brain slices
A. The presynaptic terminal expresses synaptopHluorin (spH) in synaptic vesicles. The spH fluorescence is quenched (green) inside of the acidic synaptic vesicles and increases (pink) when the synaptic vesicle lumen is exposed to the extracellular space. The spH remains within a presynaptic terminal during the synaptic vesicle cycle. B, C. Changes in spH fluorescence in CA3 presynaptic boutons (white circles) before (1), during (2), after (3) synaptic stimulation and after application of NH4Cl (4) in the hippocampal slices. Scale bars: vertical,10%; horizontal, 5 sec.
Figure 4
Figure 4. Simultaneous monitoring of synaptic strength and presynaptic function during LTP
A. Presynaptic function, as indicated by peak ΔF, was slowly enhanced during compound LTP induced by 200-Hz tetanization. B. NMDAR-LTP induced by 50-Hz tetanization resulted in a lack of presynaptic enhancement.
Figure 5
Figure 5. Models of NMDAR-LTP and compound LTP at CA3-CA1 synapses
Top panel. A synapse before LTP occurs. Bottom left panel. Weak-induction protocols produce postsynaptic NMDAR-LTP. Calcium enters the postsynaptic dendritic spine via NMDARs (blue) and triggers the insertion of AMPARs (green) onto the postsynaptic plasma membrane. Bottom right panel. Strong-induction protocols produce compound LTP. During compound LTP, calcium enters the postsynaptic dendritic spine via NMDARs and L-VGCCs (pink). Calcium entering through L-VGCCs is used to generate a retrograde signal, which enhances presynaptic function.
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References

    1. Araki R, Sakagami H, Yanagawa Y, Hikima T, Ishizuka T, Yawo H. Transgenic mouse lines expressing synaptopHluorin in hippocampus and cerebellar cortex. Genesis. 2005;42:53–60. - PubMed
    1. Bagal AA, Kao JP, Tang CM, Thompson SM. Long-term potentiation of exogenous glutamate responses at single dendritic spines. Proc Natl Acad Sci U S A. 2005;102:14434–9. - PMC - PubMed
    1. Balaji J, Ryan TA. Single-vesicle imaging reveals that synaptic vesicle exocytosis and endocytosis are coupled by a single stochastic mode. Proc Natl Acad Sci U S A. 2007;104:20576–81. - PMC - PubMed
    1. Bannerman DM, Good MA, Butcher SP, Ramsay M, Morris RG. Distinct components of spatial learning revealed by prior training and NMDA receptor blockade. Nature. 1995;378:182–6. - PubMed
    1. Baudry M, Lynch G. Remembrance of arguments past: how well is the glutamate receptor hypothesis of LTP holding up after 20 years? Neurobiol Learn Mem. 2001;76:284–97. - PubMed

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