title: Rapid erasure of hippocampal memory following inhibition of dentate gyrus granule cells.
abstract: The hippocampus is critical for the acquisition and retrieval of episodic and contextual memories. Lesions of the dentate gyrus, a principal input of the hippocampus, block memory acquisition, but it remains unclear whether this region also plays a role in memory retrieval. Here we combine cell-type specific neural inhibition with electrophysiological measurements of learning-associated plasticity in behaving mice to demonstrate that dentate gyrus granule cells are not required for memory retrieval, but instead have an unexpected role in memory maintenance. Furthermore, we demonstrate the translational potential of our findings by showing that pharmacological activation of an endogenous inhibitory receptor expressed selectively in dentate gyrus granule cells can induce a rapid loss of hippocampal memory. These findings open a new avenue for the targeted erasure of episodic and contextual memories.
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), via Ramarini 32, Monterotondo 00015, Italy.|Division of Neuroscience, University Pablo Olavide, Carretera de Utrera-km 1, Sevilla 41013, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Madroñal
authors.affiliation: Division of Neuroscience, University Pablo Olavide, Carretera de Utrera-km 1, Sevilla 41013, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Delgado-García
authors.affiliation: Division of Neuroscience, University Pablo Olavide, Carretera de Utrera-km 1, Sevilla 41013, Spain.
authors.forename: Azahara
authors.initials: A
authors.lastname: Fernández-Guizán
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chatterjee
authors.affiliation: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: Köhn
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), via Ramarini 32, Monterotondo 00015, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Mattucci
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), via Ramarini 32, Monterotondo 00015, Italy.
authors.forename: Apar
authors.initials: A
authors.lastname: Jain
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), via Ramarini 32, Monterotondo 00015, Italy.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Tsetsenis
authors.affiliation: Schaller Research Group on Neuropeptides, German Cancer Research Center DKFZ, Central Institute of Mental Health, CellNetwork Cluster of Excellence, University of Heidelberg, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Illarionova
authors.affiliation: Schaller Research Group on Neuropeptides, German Cancer Research Center DKFZ, Central Institute of Mental Health, CellNetwork Cluster of Excellence, University of Heidelberg, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Valery
authors.initials: V
authors.lastname: Grinevich
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), via Ramarini 32, Monterotondo 00015, Italy.
authors.forename: Cornelius T
authors.initials: CT
authors.lastname: Gross
authors.affiliation: Division of Neuroscience, University Pablo Olavide, Carretera de Utrera-km 1, Sevilla 41013, Spain.
authors.forename: Agnès
authors.initials: A
authors.lastname: Gruart
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D003213:Conditioning, Psychological; D018891:Dentate Gyrus / Q000166:cytology*; D018728:Entorhinal Cortex / Q000502:physiology; D005260:Female; D008297:Male; D008568:Memory / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D015398:Signal Transduction; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D000241:Adenosine