title: Forgetting of long-term memory requires activation of NMDA receptors, L-type voltage-dependent Ca2+ channels, and calcineurin.
abstract: In the past decades, the cellular and molecular mechanisms underlying memory consolidation, reconsolidation, and extinction have been well characterized. However, the neurobiological underpinnings of forgetting processes remain to be elucidated. Here we used behavioral, pharmacological and electrophysiological approaches to explore mechanisms controlling forgetting. We found that post-acquisition chronic inhibition of the N-methyl-D-aspartate receptor (NMDAR), L-type voltage-dependent Ca(2+) channel (LVDCC), and protein phosphatase calcineurin (CaN), maintains long-term object location memory that otherwise would have been forgotten. We further show that NMDAR activation is necessary to induce forgetting of object recognition memory. Studying the role of NMDAR activation in the decay of the early phase of long-term potentiation (E-LTP) in the hippocampus, we found that ifenprodil infused 30 min after LTP induction in vivo blocks the decay of CA1-evoked postsynaptic plasticity, suggesting that GluN2B-containing NMDARs activation are critical to promote LTP decay. Taken together, these findings indicate that a well-regulated forgetting process, initiated by Ca(2+) influx through LVDCCs and GluN2B-NMDARs followed by CaN activation, controls the maintenance of hippocampal LTP and long-term memories over time.
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: Fabiana
authors.initials: F
authors.lastname: Santana
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: Ana Paula
authors.initials: AP
authors.lastname: Crestani
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
authors.initials: P
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.
authors.forename: Lizeth Katherine
authors.initials: LK
authors.lastname: Pedraza
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: Jorge Alberto
authors.initials: JA
authors.lastname: Quillfeldt
authors.affiliation: Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh, Scotland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hardt
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.|Laboratório de Neurobiologia da Memória, Departamento de Biofísica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves 9500, Prédio 43422, Sala 216A, CEP 91.501-970, Porto Alegre, Rio Grande do Sul, Brasil.
authors.forename: Lucas de Oliveira
authors.initials: Lde O
authors.lastname: Alvares
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D019703:Calcineurin / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D055366:Synaptic Potentials / Q000187:drug effects
chemical_list: D020746:Calcium Channels, L-Type; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D019703:Calcineurin; C010739:ifenprodil