title: Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene.
abstract: Behavioral symptoms in individuals with autism spectrum disorder (ASD) have been attributed to abnormal neuronal connectivity, but the molecular bases of these behavioral and brain phenotypes are largely unknown. Human genetic studies have implicated PCDH10, a member of the δ2 subfamily of nonclustered protocadherin genes, in ASD. PCDH10 expression is enriched in the basolateral amygdala, a brain region implicated in the social deficits of ASD. Previous reports indicate that Pcdh10 plays a role in axon outgrowth and glutamatergic synapse elimination, but its roles in social behaviors and amygdala neuronal connectivity are unknown. We hypothesized that haploinsufficiency of Pcdh10 would reduce social approach behavior and alter the structure and function of amygdala circuits.
  
  
  
  Mice lacking one copy of Pcdh10 (Pcdh10+/-) and wild-type littermates were assessed for social approach and other behaviors. The lateral/basolateral amygdala was assessed for dendritic spine number and morphology, and amygdala circuit function was studied using voltage-sensitive dye imaging. Expression of Pcdh10 and N-methyl-D-aspartate receptor (NMDAR) subunits was assessed in postsynaptic density fractions of the amygdala.
  
  
  
  Male Pcdh10+/-mice have reduced social approach behavior, as well as impaired gamma synchronization, abnormal spine morphology, and reduced levels of NMDAR subunits in the amygdala. Social approach deficits in Pcdh10+/-male mice were rescued with acute treatment with the NMDAR partial agonist d-cycloserine.
  
  
  
  Our studies reveal that male Pcdh10+/-mice have synaptic and behavioral deficits, and establish Pcdh10+/-mice as a novel genetic model for investigating neural circuitry and behavioral changes relevant to ASD.
authors: Cell and Molecular Biology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Hannah
authors: H
authors: Schoch
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Arati S
authors: AS
authors: Kreibich
authors: Department of Biology, University of Pennsylvania, Philadelphia.
authors: Sarah L
authors: SL
authors: Ferri
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Rachel S
authors: RS
authors: White
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Dominique
authors: D
authors: Bohorquez
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Anamika
authors: A
authors: Banerjee
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Russell G
authors: RG
authors: Port
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Holly C
authors: HC
authors: Dow
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Lucero
authors: L
authors: Cordero
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Ashley A
authors: AA
authors: Pallathra
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Hyong
authors: H
authors: Kim
authors: Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Hongzhe
authors: H
authors: Li
authors: Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Warren B
authors: WB
authors: Bilker
authors: Department of Cell Biology, Kansai Medical University, Osaka, Japan.
authors: Shinji
authors: S
authors: Hirano
authors: Department of Psychiatry,Perelman School of Medicine at the University of Pennsylvania, Philadelphia; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia; Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors: Robert T
authors: RT
authors: Schultz
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia; Department of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors: Karin
authors: K
authors: Borgmann-Winter
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Chang-Gyu
authors: CG
authors: Hahn
authors: Institute of Neuroscience and Medicine, Forschungzentrum Julich, Julich; Department of Psychiatry, Psychotherapy and Psychosomatics, Medical School, RWTH Aachen University, Aachen, Germany.
authors: Dirk
authors: D
authors: Feldmeyer
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors: Gregory C
authors: GC
authors: Carlson
authors: Department of Biology, University of Pennsylvania, Philadelphia.
authors: Ted
authors: T
authors: Abel
authors: Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. Electronic address: ebrodkin@mail.med.upenn.edu.
authors: Edward S
authors: ES
authors: Brodkin
mesh_terms: D000679:Amygdala / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D001522:Behavior, Animal / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D049229:Dendritic Spines / Q000473:pathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D065818:Gamma Rhythm; D057895:Haploinsufficiency; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D057907:Post-Synaptic Density / Q000378:metabolism; D000091363:Protocadherins; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology; D012919:Social Behavior; D014828:Vocalization, Animal
chemical_list: D015820:Cadherins; D009419:Nerve Tissue Proteins; D000091363:Protocadherins; D016194:Receptors, N-Methyl-D-Aspartate; C121673:Gprin1 protein, mouse; C117277:Pcdh10 protein, mouse
keywords: Amygdala; Autism; Gene; NMDA; Protocadherin; Synapse