TABLE 3.
Molecular pathways of LTP/spine enlargement and LTD/spine shrinkage.
| Molecule | LTP/spine enlargement | LTD/spine shrinkage |
| NMDAR GABA-R (involved in LTD) (mGluR—shrinkage of large spines) |
Ca2+ increase → CaMKII activation |
Ca2+ concentration regulation, calcineurin activation |
| CaMKII | small GTPase activation; AMPAR regulation; NMDAR stabilization; |
AMPAR regulation |
| Rac GTPase | regulation of actin binding proteins, Arp2/3 and cofilin, via WAVE and PAK-LIMK pathways, respectively; AMPAR regulation |
|
| Cdc42 | regulation of actin binding proteins, Arp2/3 and cofilin, via WASP and PAK-LIMK pathways, respectively; support of hippocampal LTP |
|
| Calcineurin | actin depolymerization e.g., via cofilin; AMPAR dephosphorylation |
|
| p38 MAPK | actin depolymerization through activation of cofilin via MAPK-activated protein kinase 2; AMPAR endocytosis |
Overview of some molecules that exert effects on both structural and functional plasticity (left column).
The middle column indicates the role of these molecules in LTP and dendritic spine enlargement, while the right column describes the effects of molecules involved in LTD and spine shrinkage [based on Okamoto et al. (2004); Holbro et al. (2009); Baumgärtel and Mansuy (2012); Bosch and Hayashi (2012); Coultrap and Bayer (2012); Hayama et al. (2013); Oh et al. (2013); Kim et al. (2014); Nishiyama and Yasuda (2015); Borovac et al. (2018); Woolfrey et al. (2018); Zhang et al. (2018); Nishiyama (2019); Stein and Zito (2019); Costa et al. (2020); Runge et al. (2020); Stein et al. (2020); and Suratkal et al. (2021)].
AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; Arp, actin-related protein; CaMKII, calcium calmodulin kinase II; Cdc42, cell division control protein-42 homolog; GABA-R, gamma-aminobutyric acid receptor; GTP, guanosine triphosphate; LIMK, LIM kinase, MAPK, mitogen-activated protein kinase; mGluR, metabotropic glutamate receptor; NMDAR, N-Methyl-D-aspartate receptor; PAK, p21-activated kinase; WASP, Wiskott-Aldrich syndrome protein; WAVE, WASP family verprolin homologous (protein).