Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene.

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TitleSociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene.
Publication TypeJournal Article
Year of Publication2017
AuthorsSchoch, H, Kreibich, AS, Ferri, SL, White, RS, Bohorquez, D, Banerjee, A, Port, RG, Dow, HC, Cordero, L, Pallathra, AA, Kim, H, Li, H, Bilker, WB, Hirano, S, Schultz, RT, Borgmann-Winter, K, Hahn, C-G, Feldmeyer, D, Carlson, GC, Abel, T, Brodkin, ES
JournalBiol Psychiatry
Volume81
Issue3
Pagination193-202
Date Published2017 02 01
ISSN1873-2402
KeywordsAmygdala, Animals, Autism Spectrum Disorder, Behavior, Animal, Cadherins, Dendritic Spines, Disease Models, Animal, Electric Stimulation, Female, Gamma Rhythm, Haploinsufficiency, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Nerve Tissue Proteins, Post-Synaptic Density, Receptors, N-Methyl-D-Aspartate, Social Behavior, Vocalization, Animal
Abstract

BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.

DOI10.1016/j.biopsych.2016.06.008
Alternate JournalBiol. Psychiatry
PubMed ID27567313
PubMed Central IDPMC5161717
Grant ListP50 MH096891 / MH / NIMH NIH HHS / United States
R01 MH080718 / MH / NIMH NIH HHS / United States
T32 MH017168 / MH / NIMH NIH HHS / United States
T32 NS007413 / NS / NINDS NIH HHS / United States
/ RA / ARRA NIH HHS / United States