Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams

Summary: The organization of fear memory involves the participation of multiple brain regions. However, it is largely unknown how fear memory is formed, which circuit pathways are used for “printing” memory engrams across brain regions, and the role of identified brain circuits in memory retrieval....

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Main Authors: Ilaria Bertocchi, Florbela Rocha-Almeida, María Teresa Romero-Barragán, Marco Cambiaghi, Alejandro Carretero-Guillén, Paolo Botta, Godwin K. Dogbevia, Mario Treviño, Paolo Mele, Alessandra Oberto, Matthew E. Larkum, Agnes Gruart, Rolf Sprengel, José Maria Delgado-García, Mazahir T. Hasan
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223021272
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author Ilaria Bertocchi
Florbela Rocha-Almeida
María Teresa Romero-Barragán
Marco Cambiaghi
Alejandro Carretero-Guillén
Paolo Botta
Godwin K. Dogbevia
Mario Treviño
Paolo Mele
Alessandra Oberto
Matthew E. Larkum
Agnes Gruart
Rolf Sprengel
José Maria Delgado-García
Mazahir T. Hasan
author_facet Ilaria Bertocchi
Florbela Rocha-Almeida
María Teresa Romero-Barragán
Marco Cambiaghi
Alejandro Carretero-Guillén
Paolo Botta
Godwin K. Dogbevia
Mario Treviño
Paolo Mele
Alessandra Oberto
Matthew E. Larkum
Agnes Gruart
Rolf Sprengel
José Maria Delgado-García
Mazahir T. Hasan
author_sort Ilaria Bertocchi
collection DOAJ
description Summary: The organization of fear memory involves the participation of multiple brain regions. However, it is largely unknown how fear memory is formed, which circuit pathways are used for “printing” memory engrams across brain regions, and the role of identified brain circuits in memory retrieval. With advanced genetic methods, we combinatorially blocked presynaptic output and manipulated N-methyl-D-aspartate receptor (NMDAR) in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) before and after cued fear conditioning. Further, we tagged fear-activated neurons during associative learning for optogenetic memory recall. We found that presynaptic mPFC and postsynaptic BLA NMDARs are required for fear memory formation, but not expression. Our results provide strong evidence that NMDAR-dependent synaptic plasticity drives multi-trace systems consolidation for the sequential printing of fear memory engrams from BLA to mPFC and, subsequently, to the other regions, for flexible memory retrieval.
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spelling doaj.art-eef971ec2bee4393bdea89beefd17a002023-10-15T04:38:04ZengElsevieriScience2589-00422023-11-012611108050Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engramsIlaria Bertocchi0Florbela Rocha-Almeida1María Teresa Romero-Barragán2Marco Cambiaghi3Alejandro Carretero-Guillén4Paolo Botta5Godwin K. Dogbevia6Mario Treviño7Paolo Mele8Alessandra Oberto9Matthew E. Larkum10Agnes Gruart11Rolf Sprengel12José Maria Delgado-García13Mazahir T. Hasan14Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany; Department of Neuroscience ''Rita Levi Montalcini'', Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, 10043 Turin, Italy; Corresponding authorDivision of Neurosciences, University Pablo de Olavide, Ctra. de Utrera, km. 1 41013 Seville, SpainDivision of Neurosciences, University Pablo de Olavide, Ctra. de Utrera, km. 1 41013 Seville, SpainDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada le Grazie 8, Verona, ItalyLaboratory of Brain Circuits Therapeutics, Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, Sede Building, Barrio Sarriena, s/n, 48940 Leioa, SpainCNS drug development, Copenhagen, Capital Region, DenmarkDepartment of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany; Health Canada, 70 Colombine Driveway, Ottawa, ON K1A0K9, CanadaDepartment of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany; Laboratorio de Plasticidad Cortical y Aprendizaje Perceptual, Instituto de Neurociencias, Universidad de Guadalajara, Guadalajara, MexicoDepartment of Neuroscience ''Rita Levi Montalcini'', Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, 10043 Turin, ItalyDepartment of Neuroscience ''Rita Levi Montalcini'', Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, 10043 Turin, ItalyNeuroCure, Charité-Universitatsmedizin, Virchowweg 6, 10117 Berlin, GermanyDivision of Neurosciences, University Pablo de Olavide, Ctra. de Utrera, km. 1 41013 Seville, SpainDepartment of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, GermanyDivision of Neurosciences, University Pablo de Olavide, Ctra. de Utrera, km. 1 41013 Seville, Spain; Corresponding authorDepartment of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany; Laboratory of Brain Circuits Therapeutics, Achucarro Basque Center for Neuroscience, Science Park of the UPV/EHU, Sede Building, Barrio Sarriena, s/n, 48940 Leioa, Spain; Ikerbasque – Basque Foundation for Science, Bilbao, Spain; Corresponding authorSummary: The organization of fear memory involves the participation of multiple brain regions. However, it is largely unknown how fear memory is formed, which circuit pathways are used for “printing” memory engrams across brain regions, and the role of identified brain circuits in memory retrieval. With advanced genetic methods, we combinatorially blocked presynaptic output and manipulated N-methyl-D-aspartate receptor (NMDAR) in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) before and after cued fear conditioning. Further, we tagged fear-activated neurons during associative learning for optogenetic memory recall. We found that presynaptic mPFC and postsynaptic BLA NMDARs are required for fear memory formation, but not expression. Our results provide strong evidence that NMDAR-dependent synaptic plasticity drives multi-trace systems consolidation for the sequential printing of fear memory engrams from BLA to mPFC and, subsequently, to the other regions, for flexible memory retrieval.http://www.sciencedirect.com/science/article/pii/S2589004223021272Behavioral neuroscienceCellular neuroscience
spellingShingle Ilaria Bertocchi
Florbela Rocha-Almeida
María Teresa Romero-Barragán
Marco Cambiaghi
Alejandro Carretero-Guillén
Paolo Botta
Godwin K. Dogbevia
Mario Treviño
Paolo Mele
Alessandra Oberto
Matthew E. Larkum
Agnes Gruart
Rolf Sprengel
José Maria Delgado-García
Mazahir T. Hasan
Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams
iScience
Behavioral neuroscience
Cellular neuroscience
title Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams
title_full Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams
title_fullStr Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams
title_full_unstemmed Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams
title_short Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams
title_sort pre and postsynaptic n methyl d aspartate receptors are required for sequential printing of fear memory engrams
topic Behavioral neuroscience
Cellular neuroscience
url http://www.sciencedirect.com/science/article/pii/S2589004223021272
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