title: Forgetting of what was once learned: Exploring the role of postsynaptic ionotropic glutamate receptors on memory formation, maintenance, and decay.
abstract: Over the past years, extensive research in experimental cognitive neuroscience has provided a comprehensive understanding about the role of ionotropic glutamate receptor (IGluR)-dependent signaling underpinning postsynaptic plasticity induced by long-term potentiation (LTP), the leading cellular basis of long-term memory (LTM). However, despite the fact that iGluR-mediated postsynaptic plasticity regulates the formation and persistence of LTP and LTM, here we discuss the state-of-the-art regarding the mechanisms underpinning both LTP and LTM decay. First, we review the crucial roles that iGluRs play on memory encoding and stabilization. Second, we discuss the latest findings in forgetting considering hippocampal GluA2-AMPAR trafficking at postsynaptic sites as well as dendritic spine remodeling possibly involved in LTP decay. Third, on the role of retrieving consolidated LTMs, we discuss the mechanisms involved in memory destabilization that occurs followed reactivation that share striking similarities with the neurobiological basis of forgetting. Fourth, since different AMPAR subunits as well as postsynaptic scaffolding proteins undergo ubiquitination, the ubiquitin-proteasome system (UPS) is discussed in light of memory decay. In conclusion, we provide an integrated overview revealing some of the mechanisms determining memory forgetting that are mediated by iGluRs. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
authors.affiliation: Neurobiology of Memory Lab, Biophysics Department, Bioscience Institute, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Graduate Program in Neuroscience, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Ricardo Marcelo
authors.initials: RM
authors.lastname: Sachser
authors.affiliation: Psychobiology and Neurocomputation Lab, Biophysics Department, Bioscience Institute, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Graduate Program in Neuroscience, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Josué
authors.initials: J
authors.lastname: Haubrich
authors.affiliation: Neurobiology of Memory Lab, Biophysics Department, Bioscience Institute, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Graduate Program in Neuroscience, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Paula Santana
authors.initials: PS
authors.lastname: Lunardi
authors.affiliation: Neurobiology of Memory Lab, Biophysics Department, Bioscience Institute, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Graduate Program in Neuroscience, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: lucas.alvares@ufrgs.br.
authors.forename: Lucas
authors.initials: L
authors.lastname: de Oliveira Alvares
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation; D057567:Memory, Long-Term / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D054875:Ubiquitination
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D046988:Proteasome Endopeptidase Complex
keywords: AMPA; Decay; Depotentiation; Glutamate; Long-term potentiation; NMDA