Hansen KB, Wollmuth LP, Bowie D, Furukawa H, Menniti FS, Sobolevsky AI et al. Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels. Pharmacol Rev [Internet]. 2021 [cited 2024 Mar 15];73:1469–658. https://pubmed.ncbi.nlm.nih.gov/34753794/

Paoletti P, Bellone C, Zhou Q. NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nat Publishing Group [Internet]. 2013;14:383–400. https://doi.org/10.1038/nrn3504. Available from: sci-hub.tw/.

Article  CAS  Google Scholar 

Wang R, Reddy PH. Role of glutamate and NMDA receptors in Alzheimer’s Disease. J Alzheimer’s Disease. 2017;57:1041–8.

Article  CAS  Google Scholar 

Chen S, Xu D, Fan L, Fang Z, Wang X, Li M. Roles of N-Methyl-D-Aspartate receptors (NMDARs) in Epilepsy. Front Mol Neurosci. 2022;14:797253.

Article  PubMed  PubMed Central  Google Scholar 

Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell [Internet]. 2012;148:1204–22. https://doi.org/10.1016/j.cell.2012.02.040

Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH. Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron [Internet]. 1994 [cited 2024 Mar 15];12:529–40. https://pubmed.ncbi.nlm.nih.gov/7512349/

Watanabe M, Inoue Y, Sakimura K, Mishina M. Distinct distributions of five N-methyl-D-aspartate receptor channel subunit mRNAs in the forebrain. J Comp Neurol [Internet]. 1993 [cited 2024 Mar 15];338:377–90. https://pubmed.ncbi.nlm.nih.gov/8113446/

Fritschy J-M, Weinmann O, Wenzel A, Benke D. Synapse-Specific Localization of NMDA and GABA A Receptor Subunits Revealed by Antigen-Retrieval Immunohistochemistry. J Comp Neurol [Internet]. 1998 [cited 2024 Mar 15];390:194–210. https://onlinelibrary.wiley.com/terms-and-conditions

Watanabe M, Fukaya M, Sakimura K, Manabe T, Mishina M, Inoue Y. Selective scarcity of NMDA receptor channel subunits in the stratum lucidum (mossy fibre-recipient layer) of the mouse hippocampal CA3 subfield. Eur J Neurosci. 1998;10:478–87.

Article  CAS  PubMed  Google Scholar 

DeCarli C, Mungas D, Harvey D, Reed B, Weiner M, Chui H et al. Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia. Neurology [Internet]. 2004 [cited 2024 Mar 15];63:220–7. https://pubmed.ncbi.nlm.nih.gov/15277612/

Lacy JW, Yassa MA, Stark SM, Muftuler LT, Stark CEL. Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity. Learn Mem [Internet]. 2010 [cited 2024 Mar 15];18:15–8. https://pubmed.ncbi.nlm.nih.gov/21164173/

Yassa MA, Stark SM, Bakker A, Albert MS, Gallagher M, Stark CEL. High-resolution structural and functional MRI of hippocampal CA3 and dentate gyrus in patients with amnestic Mild Cognitive Impairment. Neuroimage [Internet]. 2010 [cited 2024 Mar 15];51:1242–52. https://pubmed.ncbi.nlm.nih.gov/20338246/

Takumi Y, Ramírez-León V, Laake P, Rinvik E, Ottersen OP. Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat Neurosci. 1999;2:618–24.

Article  CAS  PubMed  Google Scholar 

Racca C, Stephenson FA, Streit P, Roberts JDB, Somogyi P. NMDA receptor content of synapses in stratum radiatum of the hippocampal CA1 area. J Neurosci. 2000;20:2512–22.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nyíri G, Stephenson FA, Freund TF, Somogyi P. Large variability in synaptic N-methyl-D-aspartate receptor density on interneurons and a comparison with pyramidal-cell spines in the rat hippocampus. Neuroscience [Internet]. 2003 [cited 2024 Mar 15];119:347–63. https://pubmed.ncbi.nlm.nih.gov/12770551/

Berg LK, Larsson M, Morland C, Gundersen V. Pre- and postsynaptic localization of NMDA receptor subunits at hippocampal mossy fibre synapses. Neuroscience [Internet]. 2013 [cited 2024 Mar 15];230:139–50. https://pubmed.ncbi.nlm.nih.gov/23159309/

Bashir ZI, Alford S, Davies SN, Randall AD, Collingridge GL. Long-term potentiation of NMDA receptor-mediated synaptic transmission in the hippocampus. Nature [Internet]. 1991 [cited 2024 Mar 15];349:156–8. https://pubmed.ncbi.nlm.nih.gov/1846031/

Rebola N, Lujan R, Cunha RA, Mulle C. Adenosine A2A receptors are essential for long-term potentiation of NMDA-EPSCs at hippocampal mossy fiber synapses. Neuron [Internet]. 2008 [cited 2024 Mar 15];57:121–34. https://pubmed.ncbi.nlm.nih.gov/18184569/

Morris RGM, Anderson E, Lynch GS, Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature [Internet]. 1986 [cited 2024 Mar 15];319:774–6. https://pubmed.ncbi.nlm.nih.gov/2869411/

Selkoe DJ. Alzheimer’s Disease Is a Synaptic Failure. Science (1979) [Internet]. 2002;298:789–91. https://www.science.org/doi/https://doi.org/10.1126/science.1074069

Alfaro-Ruiz R, Aguado C, Martín-Belmonte A, Moreno-Martínez AE, Merchán-Rubira J, Hernández F et al. Different modes of synaptic and extrasynaptic NMDA receptor alteration in the hippocampus of P301S tau transgenic mice. Brain Pathol [Internet]. 2023 [cited 2024 Mar 15];33. https://pubmed.ncbi.nlm.nih.gov/36058615/

Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, Borchelt DR. Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng [Internet]. 2001;17:157–65. https://linkinghub.elsevier.com/retrieve/pii/S1389034401000673

Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet [Internet]. 2004 [cited 2024 Mar 15];13:159–70. https://pubmed.ncbi.nlm.nih.gov/14645205/

Garcia-Alloza M, Robbins EM, Zhang-Nunes SX, Purcell SM, Betensky RA, Raju S, et al. Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol Dis. 2006;24:516–24.

Article  CAS  PubMed  Google Scholar 

Gimbel DA, Nygaard HB, Coffey EE, Gunther EC, Laurén J, Gimbel ZA, et al. Memory impairment in transgenic alzheimer mice requires cellular prion protein. J Neurosci. 2010;30:6367–74.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Siegel SJ, Brose N, Janssen WG, Gasic GP, Jahn R, Heinemann SF et al. Regional, cellular, and ultrastructural distribution of N-methyl-D-aspartate receptor subunit 1 in monkey hippocampus. Proc Natl Acad Sci U S A [Internet]. 1994 [cited 2024 Mar 15];91:564–8. https://europepmc.org/articles/PMC42989

Aguado C, Martín-Belmonte A, Alfaro-Ruiz R, Martínez-Moreno AE, Luján R, Histoblot. A sensitive method to quantify the expression of proteins in normal and pathological conditions. Histol Histopathol [Internet]. 2023 [cited 2024 Mar 15];38:725–37. https://pubmed.ncbi.nlm.nih.gov/36648032/

Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, de la Ossa L, Martínez-Hernández J et al. Reduction in the neuronal surface of post and presynaptic GABAB receptors in the hippocampus in a mouse model of Alzheimer’s disease. Brain Pathol [Internet]. 2020 [cited 2024 Mar 15];30:554–75. https://pubmed.ncbi.nlm.nih.gov/31729777/

Tanaka JI, Matsuzaki M, Tarusawa E, Momiyama A, Molnar E, Kasai H, et al. Number and density of AMPA receptors in single synapses in immature cerebellum. J Neurosci. 2005;25:799–807.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luján R, Aguado C, Ciruela F, Cózar J, Kleindienst D, de la Ossa L, et al. Differential association of GABA B receptors with their effector ion channels in Purkinje cells. Brain Struct Funct. 2018;223:1565–87.

Article  PubMed  Google Scholar 

Chicurel ME, Harris KM. Three-dimensional analysis of the structure and composition of CA3 branched dendritic spines and their synaptic relationships with mossy fiber boutons in the rat hippocampus. Journal of Comparative Neurology [Internet]. 1992 [cited 2024 Jun 14];325:169–82. https://onlinelibrary.wiley.com/doi/full/https://doi.org/10.1002/cne.903250204

Chen Y, Fu AKY, Ip NY. Synaptic dysfunction in Alzheimer’s disease: Mechanisms and therapeutic strategies. Pharmacol Ther [Internet]. 2019 [cited 2024 Mar 15];195:186–98. https://pubmed.ncbi.nlm.nih.gov/30439458/

Meftah S, Gan J. Alzheimer’s disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression. Front Synaptic Neurosci [Internet]. 2023 [cited 2024 Mar 15];15. https://pubmed.ncbi.nlm.nih.gov/36970154/

Malinow R. New developments on the role of NMDA receptors in Alzheimer’s disease. Curr Opin Neurobiol [Internet]. 2012 [cited 2024 Mar 15];22:559–63. https://pubmed.ncbi.nlm.nih.gov/21962484/

Avila J, Llorens-Martín M, Pallas-Bazarra N, Bolós M, Perea JR, Rodríguez-Matellán A et al. Cognitive Decline in Neuronal Aging and Alzheimer’s Disease: Role of NMDA Receptors and Associated Proteins. Front Neurosci [Internet]. 2017 [cited 2024 Mar 15];11:626. /pmc/articles/PMC5687061/

Volianskis A, Køstner R, Mølgaard M, Hass S, Jensen MS. Episodic memory deficits are not related to altered glutamatergic synaptic transmission and plasticity in the CA1 hippocampus of the APPswe/PS1δE9-deleted transgenic mice model of ß-amyloidosis. Neurobiol Aging [Internet]. 2010 [cited 2024 Mar 15];31:1173–87. https://pubmed.ncbi.nlm.nih.gov/18790549/

Hynd MR, Scott HL, Dodd PR. Selective loss of NMDA receptor NR1 subunit isoforms in Alzheimer’s disease. J Neurochem [Internet]. 2004 [cited 2024 Mar 15];89:240–7. https://pubmed.ncbi.nlm.nih.gov/15030408/

Hynd MR, Scott HL, Dodd PR. Glutamate(NMDA) receptor NR1 subunit mRNA expression in Alzheimer’s disease. J Neurochem [Internet]. 2001 [cited 2024 Mar 15];78:175–82. https://pubmed.ncbi.nlm.nih.gov/11432984/

Jacob CP, Koutsilieri E, Bartl J, Neuen-Jacob E, Arzberger T, Zander N et al. Alterations in expression of glutamatergic transporters and receptors in sporadic Alzheimer’s disease. J Alzheimers Dis [Internet]. 2007 [cited 2024 Mar 15];11:97–116. https://pubmed.ncbi.nlm.nih.gov/17361039/

Bi H, Sze CI. N-methyl-D-aspartate receptor subunit NR2A and NR2B messenger RNA levels are altered in the hippocampus and entorhinal cortex in Alzheimer’s disease. J Neurol Sci [Internet]. 2002 [cited 2024 Mar 15];200:11–8. https://pubmed.ncbi.nlm.nih.gov/12127670/

Yeung JHY, Walby JL, Palpagama TH, Turner C, Waldvogel HJ, Faull RLM et al. Glutamatergic receptor expression changes in the Alzheimer’s disease hippocampus and entorhinal cortex. Brain Pathology [Internet]. 2021 [cited 2024 Mar 15];31:13005. /pmc/articles/PMC8549033/

Viana Da Silva S, Zhang P, Haberl MG, Labrousse V, Grosjean N, Blanchet C et al. Hippocampal Mossy Fibers Synapses in CA3 Pyramidal Cells Are Altered at an Early Stage in a Mouse Model of Alzheimer’s Disease. J Neurosci [Internet]. 2019 [cited 2024 Mar 15];39:4193–205. https://pubmed.ncbi.nlm.nih.gov/30886015/

Xu L, Zhou Y, Hu L, Jiang H, Dong Y, Shen H et al. Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease. Front Aging Neurosci [Internet]. 2021 [cited 2024 Mar 15];13. https://pubmed.ncbi.nlm.nih.gov/34916926/

Sze CI, Bi H, Kleinschmidt-DeMasters BK, Filley CM, Martin LJ. N-Methyl-D-aspartate receptor subunit proteins and their phosphorylation status are altered selectively in Alzheimer’s disease. J Neurol Sci [Internet]. 2001 [cited 2024 Mar 15];182:151–9. https://pubmed.ncbi.nlm.nih.gov/11137521/

Driscoll I, Howard SR, Stone JC, Monfils MH, Tomanek B, Brooks WM et al. The aging hippocampus: a multi-level analysis in the rat. Neuroscience [Internet]. 2006 [cited 2024 Mar 15];139:1173–85. https://pubmed.ncbi.nlm.nih.gov/16564634/

Oh MM, Disterhoft JF. Learning and aging affect neuronal excitability and learning. Neurobiol Learn Mem [Internet]. 2020 [cited 2024 Mar 15];167. https://pubmed.ncbi.nlm.nih.gov/31786311/

Kumar A. NMDA Receptor Function During Senescence: Implication on Cognitive Performance. Front Neurosci [Internet]. 2015 [cited 2024 Mar 15];9. https://pubmed.ncbi.nlm.nih.gov/26732087/

Amar F, Sherman MA, Rush T, Larson M, Boyle G, Chang L et al. The amyloid-β oligomer Aβ*56 induces specific alterations in neuronal signaling that lead to tau phosphorylation and aggregation. Sci Signal [Internet]. 2017 [cited 2024 Mar 15];10. https://pubmed.ncbi.nlm.nih.gov/28487416/

Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-β protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci. 2007;27:2866–75.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lacor PN, Buniel MC, Furlow PW, Sanz Clemente A, Velasco PT, Wood M et al. Aβ Oligomer-Induced Aberrations in Synapse Composition, Shape, and Density Provide a Molecular Basis for Loss of Connectivity in Alzheimer’s Disease. Journal of Neuroscience [Internet]. 2007;27:796–807. http://www.jneurosci.org/cgi/doi/https://doi.org/10.1523/JNEUROSCI.3501-06.2007

Amaral DG. Emerging principles of intrinsic hippocampal organization. Curr Opin Neurobiol [Internet]. 1993 [cited 2024 Mar 15];3:225–9. https://pubmed.ncbi.nlm.nih.gov/8390320/

Tanaka JI, Matsuzaki M, Tarusawa E, Momiyama A, Molnar E, Kasai H et al. Number and density of AMPA receptors in single synapses in immature cerebellum. J Neurosci [Internet]. 2005 [cited 2022 Sep 27];25:799–807. https://pubmed.ncbi.nlm.nih.gov/15673659/

Antal M, Fukazawa Y, Eördögh M, Muszil D, Molnár E, Itakura M et al. Numbers, densities, and colocalization of AMPA- and NMDA-type glutamate receptors at individual synapses in the superficial spinal dorsal horn of rats. J Neurosci [Internet]. 2008 [cited 2022 Sep 26];28:9692–701. https://pubmed.ncbi.nlm.nih.gov/18815255/

Sanderson TM, Georgiou J, Collingridge GL. Illuminating Relationships Between the Pre- and Post-synapse. Front Neural Circuits [Internet]. 2020 [cited 2024 Mar 15];14. https://pubmed.ncbi.nlm.nih.gov/32308573/

Llorens-Martín M, Blazquez-Llorca L, Benavides-Piccione R, Rabano A, Hernandez F, Avila J, et al. Selective alterations of neurons and circuits related to early memory loss in Alzheimer’s disease. Front Neuroanat. 2014;8:1–12.

Google Scholar 

Fouquet M, Desgranges B, La Joie R, Rivière D, Mangin JF, Landeau B et al. Role of hippocampal CA1 atrophy in memory encoding deficits in amnestic Mild Cognitive Impairment. Neuroimage [Internet]. 2012 [cited 2024 Mar 15];59:3309–15. https://pubmed.ncbi.nlm.nih.gov/22119654/

Verret L, Mann EO, Hang GB, Barth AMI, Cobos I, Ho K et al. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell [Internet]. 2012 [cited 2024 Mar 15];149:708–21. https://pubmed.ncbi.nlm.nih.gov/22541439/

Hascup KN, Findley CA, Sime LN, Hascup ER. Hippocampal alterations in glutamatergic signaling during amyloid progression in AβPP/PS1 mice. Sci Rep [Internet]. 2020 [cited 2024 Mar 15];10. https://pubmed.ncbi.nlm.nih.gov/32879385/

Huijbers W, Mormino EC, Schultz AP, Wigman S, Ward AM, Larvie M et al. Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression. Brain [Internet]. 2015 [cited 2024 Mar 15];138:1023–35. https://pubmed.ncbi.nlm.nih.gov/25678559/

Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Itakura M, Moreno-Martínez AE, de la Ossa L et al. Age-Dependent Shift of AMPA Receptors From Synapses to Intracellular Compartments in Alzheimer’s Disease: Immunocytochemical Analysis of the CA1 Hippocampal Region in APP/PS1 Transgenic Mouse Model. Front Aging Neurosci [Internet]. 2020 [cited 2024 Mar 15];12. https://pubmed.ncbi.nlm.nih.gov/33132900/

Rebola N, Carta M, Mulle C. Operation and plasticity of hippocampal CA3 circuits: implications for memory encoding. Nat Rev Neurosci [Internet]. 2017 [cited 2024 Mar 15];18:209–21. https://pubmed.ncbi.nlm.nih.gov/28251990/

Lituma PJ, Kwon HB, Alviña K, Luján R, Castillo PE. Presynaptic NMDA receptors facilitate short-term plasticity and BDNF release at hippocampal mossy fiber synapses. Elife [Internet]. 2021 [cited 2024 Mar 15];10. https://pubmed.ncbi.nlm.nih.gov/34061025/

Kwon HB, Castillo PE. Role of glutamate autoreceptors at hippocampal mossy fiber synapses. Neuron [Internet]. 2008 [cited 2024 Mar 15];60:1082–94. https://pubmed.ncbi.nlm.nih.gov/19109913/

Fukushima F, Nakao K, Shinoe T, Fukaya M, Muramatsu SI, Sakimura K et al. Ablation of NMDA receptors enhances the excitability of hippocampal CA3 neurons. PLoS One [Internet]. 2009 [cited 2024 Mar 15];4. https://pubmed.ncbi.nlm.nih.gov/19142228/

Witton J, Brown JT, Jones MW, Randall AD. Altered synaptic plasticity in the mossy fibre pathway of transgenic mice expressing mutant amyloid precursor protein. Mol Brain [Internet]. 2010 [cited 2024 Mar 15];3:1–7. https://molecularbrain.biomedcentral.com/articles/https://doi.org/10.1186/1756-6606-3-32

Rolls ET. The mechanisms for pattern completion and pattern separation in the hippocampus. Front Syst Neurosci [Internet]. 2013 [cited 2024 Mar 15];7. https://pubmed.ncbi.nlm.nih.gov/24198767/

Jonas P, Lisman J. Structure, function, and plasticity of hippocampal dentate gyrus microcircuits. Front Neural Circuits [Internet]. 2014 [cited 2024 Mar 15];8. https://pubmed.ncbi.nlm.nih.gov/25309334/

Förster E, Zhao S, Frotscher M. Laminating the hippocampus. Nat Rev Neurosci [Internet]. 2006 [cited 2024 Mar 15];7:259–67. https://pubmed.ncbi.nlm.nih.gov/16543914/

Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging. 2006;27:1372–84.

Article