title: Target-specific vulnerability of excitatory synapses leads to deficits in associative memory in a model of intellectual disorder.
abstract: Intellectual disorders (IDs) have been regularly associated with morphological and functional deficits at glutamatergic synapses in both humans and rodents. How these synaptic deficits may lead to the variety of learning and memory deficits defining ID is still unknown. Here we studied the functional and behavioral consequences of the ID gene il1rapl1 deficiency in mice and reported that il1rapl1 constitutive deletion alters cued fear memory formation. Combined in vivo and in vitro approaches allowed us to unveil a causal relationship between a marked inhibitory/excitatory (I/E) imbalance in dedicated amygdala neuronal subcircuits and behavioral deficits. Cell-targeted recordings further demonstrated a morpho-functional impact of the mutation at thalamic projections contacting principal cells, whereas the same afferents on interneurons are unaffected by the lack of Il1rapl1. We thus propose that excitatory synapses have a heterogeneous vulnerability to il1rapl1 gene constitutive mutation and that alteration of a subset of excitatory synapses in neuronal circuits is sufficient to generate permanent cognitive deficits.
authors: Centre National de la Recherche Scientifique CNRS UMR5297, Université de Bordeaux, 33077 Bordeaux, France.
authors: Xander
authors: X
authors: Houbaert
authors: Chun-Lei
authors: CL
authors: Zhang
authors: Frédéric
authors: F
authors: Gambino
authors: Marilyn
authors: M
authors: Lepleux
authors: Melissa
authors: M
authors: Deshors
authors: Elisabeth
authors: E
authors: Normand
authors: Florian
authors: F
authors: Levet
authors: Mariana
authors: M
authors: Ramos
authors: Pierre
authors: P
authors: Billuart
authors: Jamel
authors: J
authors: Chelly
authors: Etienne
authors: E
authors: Herzog
authors: Yann
authors: Y
authors: Humeau
mesh_terms: D000679:Amygdala / Q000166:cytology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001245:Association Learning / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology; D000075402:Channelrhodopsins; D003213:Conditioning, Psychological / Q000502:physiology; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D005239:Fear / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008607:Intellectual Disability / Q000150:complications* / Q000235:genetics; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure
chemical_list: D000779:Anesthetics, Local; D000075402:Channelrhodopsins; D018756:GABA Antagonists; D053577:Interleukin-1 Receptor Accessory Protein; D009419:Nerve Tissue Proteins; C485184:enhanced green fluorescent protein; C568303:interleukin-1 receptor accessory protein-like 1, mouse; D049452:Green Fluorescent Proteins; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
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