Age- and sex-specific fear conditioning deficits in mice lacking Pcdh10, an Autism Associated Gene

Neurobiol Learn Mem. 2021 Feb:178:107364. doi: 10.1016/j.nlm.2020.107364. Epub 2020 Dec 16.

Abstract

PCDH10 is a gene associated with Autism Spectrum Disorder. It is involved in the growth of thalamocortical projections and dendritic spine elimination. Previously, we characterized Pcdh10 haploinsufficient mice (Pcdh10+/- mice) and found male-specific social deficits and dark phase hypoactivity. Pcdh10+/- males exhibit increased dendritic spine density of immature morphology, decreased NMDAR expression, and decreased gamma synchronization in the basolateral amygdala (BLA). Here, we further characterize Pcdh10+/- mice by testing for fear memory, which relies on BLA function. We used both male and female Pcdh10+/- mice and their wild-type littermates at two ages, juvenile and adult, and in two learning paradigms, cued and contextual fear conditioning. We found that males at both ages and in both assays exhibited fear conditioning deficits, but females were only impaired as adults in the cued condition. These data are further evidence for male-specific alterations in BLA-related behaviors in Pcdh10+/- mice and suggest that these mice may be a useful model for dissecting male specific brain and behavioral phenotypes relevant to social and emotional behaviors.

Keywords: ASD; Autism; Fear conditioning; Protocadherin; Sex differences.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Autism Spectrum Disorder / genetics
  • Autism Spectrum Disorder / metabolism
  • Autism Spectrum Disorder / physiopathology
  • Basolateral Nuclear Complex / metabolism
  • Basolateral Nuclear Complex / physiopathology*
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Conditioning, Classical / physiology*
  • Dendritic Spines / genetics
  • Dendritic Spines / metabolism
  • Fear / physiology*
  • Female
  • Male
  • Mice
  • Mice, Knockout
  • Protocadherins
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Sex Factors

Substances

  • Cadherins
  • Pcdh10 protein, mouse
  • Protocadherins
  • Receptors, N-Methyl-D-Aspartate