title: Contribution of mGluR5 to pathophysiology in a mouse model of human chromosome 16p11.2 microdeletion.
abstract: Human chromosome 16p11.2 microdeletion is the most common gene copy number variation in autism, but the synaptic pathophysiology caused by this mutation is largely unknown. Using a mouse with the same genetic deficiency, we found that metabotropic glutamate receptor 5 (mGluR5)-dependent synaptic plasticity and protein synthesis was altered in the hippocampus and that hippocampus-dependent memory was impaired. Notably, chronic treatment with a negative allosteric modulator of mGluR5 reversed the cognitive deficit.
authors.affiliation: 1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [4] Department of Pathology and Laboratory Medicine, Developmental Neuroscience Program, The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Tian
authors.affiliation: 1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Stoppel
authors.affiliation: 1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Heynen
authors.affiliation: Pharmaceuticals Division, F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Lothar
authors.initials: L
authors.lastname: Lindemann
authors.affiliation: Pharmaceuticals Division, F. Hoffmann-La Roche, Basel, Switzerland.
authors.forename: Georg
authors.initials: G
authors.lastname: Jaeschke
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
authors.forename: Alea A
authors.initials: AA
authors.lastname: Mills
authors.affiliation: 1] Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Bear
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics / Q000378:metabolism; D033481:Chromosomes, Mammalian; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: C569289:2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine; D007093:Imidazoles; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5