From Synaptic Dysfunction to Memory Recovery: Ampakine Compounds as Potential Therapeutic Agents for Alzheimer's Disease

Abstract

Alzheimer's disease, a profoundly impactful neurodegenerative condition, manifests as the progressive deterioration of memory and cognitive functions. Studies have shown that memory decline is associated with a decrease in the rapid transmission of excitatory signals between neurons. The limited research on the positive impact of AMPA receptor modulation has prompted the exploration of Ampakine compounds. Ampakines enhance long-term potentiation (LTP) by activating receptors, which exists in a crucial role in memory preservation. The ability of ampakine compounds to bind to AMPA receptors and increase the expression of neurotrophic factors, such as BDNF, is believed to mitigate LTP impairment. Recent studies have demonstrated that certain ampakine compounds can enhance consciousness and memory storage by promoting the production of various neurotrophins, particularly BDNF and NGF. Previous research has shown that neurotrophins contribute to synaptogenesis, the formation of new connections between neurons, primarily through dendritic spines. Increasing synaptogenesis via dendritic spines positively impacts signal transmission and retention by strengthening neuronal connections. This review highlights the potential of ampakine compounds such as pesampator and hydroflumetazide to enhance synaptic interactions, alleviate symptoms of Alzheimer's disease, and specifically address memory loss through their effects on neurotrophins.

Keywords

• Alzheimer’s disease
• AMPA receptors
• Neurotrophins
• Synaptogenesis
• Ampakine

References

1. Ackermann, M., & Matus, A. (2003). Activity-induced targeting of profilin and stabilization of dendritic spine morphology.Natureneuroscience,6(11),1194-1200. https://doi.org/10.1038/nn1135
2. Aoki, C., Wu, K., Elste, A., Len, G. W., Lin, S. Y., McAuliffe, G., & Black, I. B. (2000). Localization of brain‐derived neurotrophic factor and TrkB receptors to postsynaptic densities of adult rat cerebral cortex. Journal of neuroscience research, 59(3), 454-463. https://doi.org/10.1002/(SICI)1097-4547(20000201)59:3%3C454::AID-JNR21%3E3.0.CO;2-H
3. Araya, R., Eisenthal, K. B., & Yuste, R. (2006).Dendritic spines linearize the summation of excitatory potentials. Proceedings of the National Academy of Sciences,103(49),18799-18804. https://doi.org/10.1073/pnas.0609225103
4. Bliss, T.V, and Collingridge, G.L. (1993). A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39.
5. Blum, R., & Konnerth, A. (2005). Neurotrophin-mediated rapid signaling in the central nervous system: mechanisms and functions. Physiology, 20(1),70-78. https://doi.org/10.1152/physiol.00042.2004
6. Bourne, J., & Harris, K. M. (2007). Do thin spines learn to be mushroom spines that remember?. Current opinion in neurobiology,17(3),381-386. https://doi.org/10.1016/j.conb.2007.04.009
7. Bramham, C. R. (2008). Local protein synthesis, actin dynamics, and LTP consolidation. Current opinion in neurobiology,18(5),524-531. https://doi.org/10.1016/j.conb.2008.09.013
8. Brogi, S., Campiani, G., Brindisi, M., & Butini, S. (2019). Allosteric modulation of ionotropic glutamate receptors: An outlook on new therapeutic approaches to treat central nervous system disorders. ACS Medicinal Chemistry Letters,10(3),228-236. https://doi.org/10.1021/acsmedchemlett.8b00450

9. Calabrese, B., Wilson, M. S., & Halpain, S. (2006). Development and regulation of dendritic spine synapses. Physiology,21(1),38-47. https://doi.org/10.1152/physiol.00042.2005
10. Chang, F. L. F., & Greenough, W. T. (1984). Transient and enduring morphological correlates of synaptic activity and efficacy change in the rat hippocampal slice. Brain research, 309(1),35-46. https://doi.org/10.1016/0006-8993(84)91008-4
11. Chapleau, C. A., Larimore, J. L., Theibert, A., & Pozzo-Miller, L. (2009). Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism. Journal of neurodevelopmental disorders,1,185-196. https://doi.org/10.1007/s11689-009-9027-6
12. Chapleau, C. A., Larimore, J. L., Theibert, A., & Pozzo-Miller, L. (2009). Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism. Journal of neurodevelopmental disorders,1,185-196. https://doi.org/10.1007/s11689-009-9027-6
13. Chen, L. Y., Rex, C. S., Casale, M. S., Gall, C. M., & Lynch, G. (2007). Changes in synaptic morphology accompany actin signaling during LTP. Journal of Neuroscience, 27(20), 5363-5372.https://doi.org/10.1523/JNEUROSCI.0164-07.2007
14. Chen, T. J., Gehler, S., Shaw, A. E., Bamburg, J. R., & Letourneau, P. C. (2006). Cdc42 participates in the regulation of ADF/cofilin and retinal growth cone filopodia by brain derived neurotrophic factor. Journal of neurobiology, 66(2),r103–114. https://doi.org/10.1002/neu.20204
15. Cohen‐Cory, S., Kidane, A. H., Shirkey, N. J., & Marshak, S. (2010). Brain‐derived neurotrophic factor and the development of structural neuronal connectivity. Developmental neurobiology,70(5),271-288. https://doi.org/10.1002/dneu.20774
16. Ding, Z. B., Wu, P., Luo, Y. X., Shi, H. S., Shen, H. W., Wang, S. J., & Lu, L. (2013). Region-specific role of Rac in nucleus accumbens core and basolateral amygdala in consolidation and reconsolidation of cocaine-associated cue memory in rats. Psychopharmacology,228,427-437. https://doi.org/10.1007/s00213-013-3050-8
17. Dunaevsky, A., Tashiro, A., Majewska, A., Mason, C., & Yuste, R. (1999). Developmental regulation of spine motility in the mammalian central nervous system. Proceedings of the National Academy of Sci ences, 96(23), 13438-13443. https://doi.org/10.1073/pnas.96.23.13438
18. Drake CT, Milner TA, Patterson SL: Ultrascructural localization of full-length TrkB immunoreactivity in rat hippocampus suggests multiple roles in modulating activity-dependent synaptic plasticity.J.Neurosci(1999)19(18):80098026.https://doi.org/10.1523/JNEUROSCI.19-18-08009.1999
19. Evans, R.H.; Watkins, J.C. Team Evans and Watkins: Excitatory amino acid research at Bristol University 1973–1981.Neuropharmacology2021 https://doi.org/10.1016/j.neuropharm.2021.108768
20. Ethell, I. M., & Pasquale, E. B. (2005). Molecular mechanisms of dendritic spine development and remodeling. Progress in neurobiology,75(3),161-ü205.https://doi.org/10.1016/j.pneurobio.2005.02.003
21. Fifkova, E. (1985). A possible mechanism of morphometric changes in dendritic spines induced by stimulation. Cellular and molecular neurobiology,5,47-63. https://doi.org/10.1007/BF00711085
22. Fischer, M., Kaech, S., Knutti, D., & Matus, A. (1998). Rapid actin-based plasticity in dendritic spines. Neuron, 20(5),847-854. https://doi.org/10.1016/S0896-6273(00)80467-5
23. Flynn, B. L. (1999). Pharmacologic management of alzheimer disease Part I: hormonal and emerging investigational drug therapies. Annals of Pharmacotherapy, 33(2), 178-187.
24. Frey, S., & Frey, J. U. (2008). ‘Synaptic tagging’and ‘cross-tagging’and related associative reinforcement processes of mfunctional plasticity as the cellular basis for memory formation. Progress in brainresearch,169,117-143. https://doi.org/10.1016/S0079-6123(07)00007-6
25. Gall, C. M. (1992). Regulation of brain neurctrophin expression by physiological activity. Trends in pharmacological sciences,13,401-403. https://doi.org/10.1016/0165-6147(92)90123-N
26. Golubeva,E.A.,Lavrov,M.I.,Radcheno,E.V.,&Palyulin,V.A.(2023). Diversity of AMPA Receptor Ligands: Chemotypes, Binding Modes, Mechanisms of Action, and Therapeutic Effects.Biomolecules, 13(1),56.https://doi.org/10.3390/biom13010056
27. Gümrü, S., & Aricioglu, F. (2012). Ampakines: Selective AMPA receptor modulators with potential benefits. Clinical and Experimental Health Sciences, 2(4), 143.
28. Webster, J., & Grossberg, G. T. (1996). Strategies for treating dementing disorders. Nursing Home Medicine, 6, 161-171.
29. Halpain, S., Spencer, K., & Graber, S. (2005). Dynamics and pathology of dendritic spines. Progress in brain research,147,29-37. https://doi.org/10.1016/S0079-6123(04)47003-4
30. Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., ... & Traynelis, S. F. (2021).Structure, function, and pharmacology of glutamate receptor ion channels. Pharmacological reviews, 73(4),1469-1658. https://doi.org/10.1124/pharmrev.120.000131
31. Hasselmo, M. E. (2006). The role of acetylcholine in learning and memory. Current opinion in neurobiology, 16(6),710-715. https://doi.org/10.1016/j.conb.2006.09.002
32. Hefti, F. (1994). Development of effective therapy for Alzheimer's disease based on neurotrophic factors. Neurobiologof aging. https://psycnet.apa.org/doi/10.1016/0197-4580(94)90204-6
33. Hosseini, R., Benton, D. C., Dunn, P. M., Jenkinson, D. H., & Moss, G. W. (2001). SK3 is an important component of K+ channels mediating the after hyperpolarization in cultured rat SCG neurones. The Journal of physiology,535(Pt2),323.https://doi.org/10.1111/j.1469-7793.2001.00323.x
34. Hydroflumethiazide (2021). In Drugs and Lactation Database (LactMed®). National Institute of Child Health and Human Development. Impey, S., Obrietan, K., Wong, S. T., Poser, S., Yano, S., Wayman, G., ... & Storm, D. R. (1998). Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation.Neuron,21(4),869-883. https://doi.org/10.1016/S0896-6273(00)80602-9
35. Isackson, P. J., Huntsman, M. M., Murray, K. D., & Gall, C. M. (1991). BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: temporal patterns of induction distinct from NGF. Neuron, 6(6), 937-948. https://doi.org/10.1016/0896-6273(91)90234-q
36. Kayaalp, O., & Farmakoloji, R. T. Y. T. (2002). Hacettepe-Taş Kitapçılık Ltd. Şti., Ankara, 829, 1177-1220.
37. Korkotian, E., Holcman, D., & Segal, M. (2004). Dynamic regulation of spine–dendrite coupling in cultured hippocampal neurons. European Journal of Neuroscience, 20(10), 2649-2663. https://doi.org/10.1111/j.1460-9568.2004.03691.x
38. Kiprianova, I., Sandkühler, J., Schwab, S., Hoyer, S., & Spranger, M. (1999). Brain-derived neurotrophic factor improves long-term potentiation and cognitive functions after transient forebrain ischemia in the rat. Experimental neurology,159(2),511-519. https://doi.org/10.1006/exnr.1999.7109
39. Kirov, S. A., Sorra, K. E., & Harris, K. M. (1999). Slices have more synapses than perfusion-fixed hippocampus from both young and mature rats. Journal of Neuroscience,19(8),2876-2886. https://doi.org/10.1523/JNEUROSCI.19-08-02876.1999
40. Kovalchuk, Y., Hanse, E., Kafitz, K. W.,&Konnerth,A. (2002). Postsynaptic Induction of BDNF-Mediated Long-TermPotentiation. Science(NewYork,N.Y.), 295(5560),1729–1734. https://doi.org/10.1126/science.1067766
41. Kuipers, S. D., & Bramham, C. R. (2006). Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. Current opinion in drug discovery and development, 9(5), 580.
42. Kramar,E.A.,Lin,B.,Rex,C.S.,Gall,C.M.,andLynch,G.(2006).Integrin-driven actin polymerization consolidates long-term potentiation. Proc. Natl. Acad. Sci.U.S.A.103,5579–5584. https://doi.org/10.1073/pnas.0601354103
43. Lauterborn, J.C.; Palmer, L.C.; Jia, Y.; Pham, D.T.; Hou, B.; Wang, W.; Trieu, B.H.; Cox, C.D.; Kantorovich, S.; Gall, C.M.;etal.Chronic ampakine treatments stimulate dendritic growth and promote learning in middle-aged rats. J. Neurosci.2016,36,1636-1646. https://doi.org/10.1523/JNEUROSCI.3157-15.2016
44. Lee, K.; Goodman, L.; Fourie, C.; Schenk, S.; Leitch, B.; Montgomery, J.M. AMPA receptors as therapeutic targets for neurological disorders. In Ion Channels as Therapeutic Targets, Part A; Donev, R., Ed.; Advances in Protein Chemistry and Structural Biology;Academic Press: Cambridge, MA, USA, 2016; Volume 103, pp. 203–261.https://doi.org/10.1016/bs.apcsb.2015.10.004
45. Lin, B., Kramár, E. A., Bi, X., Brucher, F. A., Gall, C. M., & Lynch, G. (2005). Theta stimulation polymerizes actin in dendritic spines of hippocampus. Journal of Neuroscience, 25(8), 2062- 2069. https://doi.org/10.1523/JNEUROSCI.4283-04.2005
46. Lloyd-Fox, S., Blasi, A., & Elwell, C. E. (2010). Illuminating the developing brain: the past, present and future of functional near infrared spectroscopy. Neuroscience&Biobehavioral Reviews,34(3),269-284. https://doi.org/10.1016/j.neubiorev.2009.07.008
47. Lu, Y., Christian, K., & Lu, B. (2008). BDNF: a key regulator for protein synthesis-dependent LTP and long-term-memory?.Neurobiology of learning and memory, 89(3), 312-323. https://doi.org/10.1016/j.nlm.2007.08.018
48. Lynch, G. (1998). Memory and the brain: unexpected chemistries and a new pharmacology. Neurobiology of learning and memory,70(1-2), 82-100. https://doi.org/10.1006/nlme.1998.3840
49. Lynch, G. (2004). AMPA receptor modulators as cognitive enhancers. Current opinion in pharmacology, 4(1), 4-11. https://doi.org/10.1016/j.coph.2003.09.009
50. Lynch,G.(2006).Glutamate-based therapeutic approaches: ampakines. Current opinion in pharmacology, 6(1), 82-88. https://doi.org/10.1016/j.coph.2005.09.005
51. Lynch, G., Cox, C. D., & Gall, C. M. (2014). Pharmacological enhancement of memory or cognition in normal subjects. Frontiers in systems neuroscience,8,90.https://doi.org/10.3389/fnsys.2014.00090
52. Malenka, R. C. (2003). The long-term potential of LTP. Nature Reviews Neuroscience,4(11),923-926. https://doi.org/10.1038/nrn1258
53. Majewska, A., Brown, E., Ross, J., & Yuste, R. (2000). Mechanisms of calcium decay kinetics in hippocampal spines: role of spine calcium pumps and calcium diffusion through the spine neck in biochemical compartmentalization. Journal of Neuroscience,20(5),1722-1734. https://doi.org/10.1523/JNEUROSCI.20-05-01722.2000
54. Majewska, A., Tashiro, A., & Yuste, R. (2000). Regulation of spine calcium dynamics by rapid spine motility. Journal of Neuroscience, 20(22), 8262-8268.https://doi.org/10.1523/JNEUROSCI.20-22-08262.2000
55. Matsuzaki, M., Honkura, N., Ellis-Davies, G. C., & Kasai, H. (2004). Structural basis of long-term potentiation in single dendritic spines. Nature,429(6993),761-766. https://doi.org/10.1038/nature02617
56. Mizrahi, A., Crowley, J. C., Shtoyerman, E., & Katz, L. C. (2004). High-resolution in vivo imaging of hippocampal dendrites and spines. Journal of Neuroscience, 24(13), 3147-3151.https://doi.org/10.1523/JNEUROSCI.5218-03.2004
57. Monaghan, D. T., Irvine, M. W., Costa, B. M., Fang, G., & Jane, D. E. (2012). Pharmacological modulation of NMDA receptor activity and the advent of negative and positive allosteric modulators. Neurochemistry international,61(4),581-592. https://doi.org/10.1016/j.neuint.2012.01.004
58. Noetzli, M., & Eap, C. B. (2013). Pharmacodynamic, pharmacokinetic and pharmacogenetic aspects of drugs used in the treatment of Alzheimer’s disease. Clinical pharmacokinetics, 52, 225-241. https://doi.org/10.1007/s40262-013-0038-9
59. Noguchi, J., Matsuzaki, M., Ellis-Davies, G. C., & Kasai, H. (2005). Spine-neck geometry determines NMDA receptor-dependent Ca2+ signaling in dendrites.Neuron,46(4), 609622.https://doi.org/10.1016/j.neuron.2005.03.015
60. O'Neill, M. J., Murray, T. K., Whalley, K., Ward, M. A., Hicks, C. A., Woodhouse, S., ... & Skolnick, P. (2004). Neurotrophic actions of the novel AMPA receptor potentiator, LY404187, in rodent models of Parkinson's disease. European journal of pharmacology, 486(2), 163-174. https://doi.org/10.1016/j.ejphar.2003.12.023
61. Partin, K.M. AMPA receptor potentiators: From drug design to cognitive enhancement. Curr. Opin. Pharmacol.2015,20,46–53. http://dx.doi.org/10.1016/j.coph.2014.11.002
62. Penzes, P., & Rafalovich, I. (2012). Regulation of the actin cytoskeleton in dendritic spines. Synaptic Plasticity: Dynamics, Development and Disease, 81-95.https://doi.org/10.1007/978-3-7091-0932-8_4
63. Peters, A., & Kaiserman‐Abramof, I. R. (1970).The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines. American Journal ofAnatomy,127(4),321-355. https://doi.org/10.1002/aja.1001270402
64. Ptak, C. P., Ahmed, A. H., & Oswald, R. E. (2009). Probing the allosteric modulator binding site of GluR2 with thiazide derivatives. Biochemistry, 48(36), 8594-8602. https://doi.org/10.1021/bi901127s
65. Radecki,D.T.,Brown,L.M.,Martinez,J.,&Teyler,T.J.(2005). BDNF protects against stress‐induced impairments in spatial learning and memory and LTP. Hippocampus,15(2),246-253. https://doi.org/10.1002/hypo.20048
66. Ranganathan, M., DeMartinis, N., Huguenel, B., Gaudreault, F., Bednar, M. M., Shaffer, C. L., ... & D’Souza, D. C. (2017). Attenuation of ketamine-induced impairment in verbal learning and memory in healthy volunteers by the AMPA receptor potentiator PF-04958242. Molecular psychiatry, 22(11),1633-1640. https://doi.org/10.1038/mp.2017.6
67. Reiner, A., & Levitz, J. (2018). Glutamatergic signaling in the central nervous system: ionotropic and metabotropic receptors in concert. Neuron,98(6),1080-1098. https://doi.org/10.1016/j.neuron.2018.05.018
68. Rex, C. S., Chen, L. Y., Sharma, A., Liu, J., Babayan, A. H., Gall, C. M., & Lynch, G. (2009). Different Rho GTPase–dependent signaling pathways initiate sequential steps in the consolidation of long-term potentiation. Journal of Cell Biology, 186(1),85-97. https://doi.org/10.1083/jcb.200901084
69. Rioult-Pedotti, M. S., Friedman, D., & Donoghue, J. P (2000).Learning-induced LTP in neocortex. science, 290(5491),533-536. https://doi.org/10.1126/science.290.5491.533
70. Schmid, D. A., Yang, T., Ogier, M., Adams, I., Mirakhur, Y., Wang, Q., ... & Katz, D. M. (2012). A TrkB small molecule partial agonist rescues TrkB phosphorylation deficits and improves respiratory function in a mouse model of Rett syndrome. Journal of Neuroscience,32(5),1803-1810. https://doi.org/10.1523/JNEUROSCI.0865-11.2012
71. Seese, R. R., Babayan, A. H., Katz, A. M., Cox, C. D., Lauterborn, J. C., Lynch, G., & Gall, C. M. (2012). LTP induction translocates cortactin at distant synapses in wild-type but not Fmr1 knock-out mice. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32(21), 7403–7413. https://doi.org/10.1523/JNEUROSCI.0968-12.2012
72. Segal, M. (2005). Dendritic spines and long-term plasticity. Nature Reviews Neuroscience,6(4),277-284. https://doi.org/10.1038/nrn1649
73. Shaffer, C. L., Patel, N. C., Schwarz, J., Scialis, R. J., Wei, Y., Hou, X. J.,... & O’Donnell, C. J. (2015). The Discovery and Characterization of the α-Amino-3-hydroxy-5-methyl-4-oxazolepropionic Acid (AMPA) Receptor Potentiator N-{(3S,4S)-4-[4-(5-Cyano-2-thienyl)phenoxy]tetrahydrofuran-3-yl}propane-2-sulfonamide(PF 04958242). Journal of Medicinal Chemistry,58(10),4291-4308. https://doi.org/10.1021/acs.jmedchem.5b00300
74. Staubli, U., and Lynch, G. (1987). Stable hippocampal long- term potentiation elicited by ‘theta’ pattern stimulation. BrainRes. 435, 227–234. https://doi.org/10.1016/0006-8993(87)91605-2
75. Strata, P., Morando, L., Bravin, M., & Rossi, F. (2000). Dendritic spine density in Purkinje cells. Trends in neurosciences,23(5),198. https://doi.org/10.1016/S0166-2236(00)01571-X
76. Takie N, Inamura N, Kawamura H (2004). Brain derived neuotrophic factor induces mammalian target of rapamycin-dependent local activation of translation machinery and protein synthesis in neuronal dendrites. L Neurosci24:9760-9769. https://doi.org/10.1523/JNEUROSCI.1427-04.2004
77. Tan, A. M. (2015). Dendritic spine dysgenesis in neuropathic pain. Progress in molecular biology and translational science,131,385-408. https://doi.org/10.1016/bs.pmbts.2014.12.001
78. Tan, A. M., & Waxman, S. G. (2012). Spinal cord injury, dendritic spine remodeling, and spinal memory mechanisms. Experimental neurology, 235(1),14251.https://doi.org/10.1016/j.expneurol.2011.08.026
79. Traynelis, S.F.; Wollmuth, L.P.; McBain, C.J.; Menniti, F.S.; Vance, K.M.; Ogden, K.K.; Hansen, K.B.; Yuan, H.; Myers, S.J.;Dingledine, R. Glutamate receptor ion channels: Structure, regulation, and function. Pharmacol. Rev. 2010, 62, 405–496. https://doi.org/10.1124/pr.109.002451
80. Tyler, W. J., & Pozzo-Miller, L. D. (2001). BDNF enhances quantal neurotransmitter release and increases the number of docked vesicles at the active zones of hippocampal excitatory synapses. Journal of Neuroscience, 21(12),4249-4258. https://doi.org/10.1523/JNEUROSCI.21-12-04249.2001
81. Vigers, A. J., Amin, D. S., Talley-Farnham, T. I. F. F. A. N. Y., Gorski, J. A., Xu, B. A. O. J. I., & Jones, K. (2012). Sustained expression of brain-derived neurotrophic factor is required for maintenance of dendritic spines and normal behavior. Neuroscience, 212, 1-18.https://doi.org/10.1016/j.neuroscience.2012.03.031
82. Wells*, D. G., & Fallon, J. R. (2000). In search of molecular memory: experience-driven protein synthesis. Cellular and Molecular Life Sciences CMLS,57,1335-1339. https://doi.org/10.1007/PL00000618
83. Wolpaw JR. Adaptive plasticity in the spinal stretch reflex: an accessible substrate of memory? Cell Mol Neurobiol.1985;5:147–165. https://doi.org/10.1007/BF00711090
84. Yin, Y., Edelman, G. M., & Vanderklish, P. W. (2002). The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes. Proceedings of the National Academy ofSciences,99(4),2368-2373. https://doi.org/10.1073/pnas.042693699
85. Yuste, R., & Bonhoeffer, T. (2001). Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annual review of neuroscience,24(1),1071-1089. https://doi.org/10.1146/annurev.neuro.24.1.1071
86. Ziv, N. E., & Smith, S. J. (1996). Evidence for a role of dendritic filopodia in synaptogenesis and spine formation.Neuron,17(1),91-102. https://doi.org/10.1016/S0896-6273(00)80283-4