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@ARTICLE{Schoch:827653,
author = {Schoch, Hannah and Kreibich, Arati S. and Ferri, Sarah L.
and White, Rachel S. and Bohorquez, Dominique and Banerjee,
Anamika and Port, Russell G. and Dow, Holly C. and Cordero,
Lucero and Pallathra, Ashley A. and Kim, Hyong and Li,
Hongzhe and Bilker, Warren B. and Hirano, Shinji and
Schultz, Robert T. and Borgmann-Winter, Karin and Hahn,
Chang-Gyu and Feldmeyer, Dirk and Carlson, Gregory C. and
Abel, Ted and Brodkin, Edward S.},
title = {{S}ociability {D}eficits and {A}ltered {A}mygdala
{C}ircuits in {M}ice {L}acking {P}cdh10, an {A}utism
{A}ssociated {G}ene},
journal = {Biological psychiatry},
volume = {81},
number = {3},
issn = {0006-3223},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {FZJ-2017-01767},
pages = {193 - 202},
year = {2017},
abstract = {BackgroundBehavioral 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.MethodsMice
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.ResultsMale 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.ConclusionsOur 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.},
cin = {INM-2},
ddc = {570},
cid = {I:(DE-Juel1)INM-2-20090406},
pnm = {571 - Connectivity and Activity (POF3-571)},
pid = {G:(DE-HGF)POF3-571},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000397011700007},
pubmed = {pmid:27567313},
doi = {10.1016/j.biopsych.2016.06.008},
url = {https://juser.fz-juelich.de/record/827653},
}