title: The hippocampo-amygdala control of contextual fear expression is affected in a model of intellectual disability.
abstract: The process of learning mainly depends on the ability to store new information, while the ability to retrieve this information and express appropriate behaviors are also crucial for the adaptation of individuals to environmental cues. Thereby, all three components contribute to the cognitive fitness of an individual. While a lack of behavioral adaptation is a recurrent trait of intellectually disabled patients, discriminating between memory formation, memory retrieval or behavioral expression deficits is not easy to establish. Here, we report some deficits in contextual fear behavior in knockout mice for the intellectual disability gene Il1rapl1. Functional in vivo experiments revealed that the lack of conditioned response resulted from a local inhibitory to excitatory (I/E) imbalance in basolateral amygdala (BLA) consecutive to a loss of excitatory drive onto BLA principal cells by caudal hippocampus axonal projections. A normalization of the fear behavior was obtained in adult mutant mice following opsin-based in vivo synaptic priming of hippocampo-BLA synapses in adult il1rapl1 knockout mice, indicating that synaptic efficacy at hippocampo-BLA projections is crucial for contextual fear memory expression. Importantly, because this restoration was obtained after the learning phase, our results suggest that some of the genetically encoded cognitive deficits in humans may originate from a lack of restitution of genuinely formed memories rather than an exclusive inability to store new memories.
authors.affiliation: Team Synapse in Cognition, Institut Interdisciplinaire de NeuroScience, Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, Bordeaux, France.
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Zhang
authors.affiliation: Team Synapse in Cognition, Institut Interdisciplinaire de NeuroScience, Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, Bordeaux, France.
authors.forename: Xander
authors.initials: X
authors.lastname: Houbaert
authors.affiliation: Team Synapse in Cognition, Institut Interdisciplinaire de NeuroScience, Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, Bordeaux, France.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Lepleux
authors.affiliation: Team Synapse in Cognition, Institut Interdisciplinaire de NeuroScience, Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, Bordeaux, France.|Pole In Vivo, Institut Interdisciplinaire de NeuroScience, Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, Bordeaux, France.
authors.forename: Melissa
authors.initials: M
authors.lastname: Deshors
authors.affiliation: Team Synapse in Cognition, Institut Interdisciplinaire de NeuroScience, Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, Bordeaux, France.|Pole In Vivo, Institut Interdisciplinaire de NeuroScience, Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, Bordeaux, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Normand
authors.affiliation: Team Synapse in Cognition, Institut Interdisciplinaire de NeuroScience, Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, Bordeaux, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gambino
authors.affiliation: Team Synapse in Cognition, Institut Interdisciplinaire de NeuroScience, Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, Bordeaux, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Herzog
authors.affiliation: Team Synapse in Cognition, Institut Interdisciplinaire de NeuroScience, Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, Bordeaux, France. yann.humeau@u-bordeaux.fr.|UMR5297 Institut Interdisciplinaire de NeuroScience, Centre de Génomique Fonctionnelle, 146 rue Léo Saignat, 33077, Bordeaux Cedex, France. yann.humeau@u-bordeaux.fr.
authors.forename: Yann
authors.initials: Y
authors.lastname: Humeau
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008607:Intellectual Disability / Q000235:genetics / Q000503:physiopathology*; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013569:Synapses / Q000502:physiology; D055366:Synaptic Potentials
chemical_list: D053577:Interleukin-1 Receptor Accessory Protein; C568303:interleukin-1 receptor accessory protein-like 1, mouse
keywords: Contextual fear expression; Hippocampal projections; Intellectual disability; Optogenetic