Document Detail

Sex-Dependent Behavioral Functions of the Purkinje Cell-Specific Gαi/o Binding Protein, Pcp2(L7).
MedLine Citation:
PMID:  22528962     Owner:  NLM     Status:  Publisher    
We previously reported motor and non-motor enhancements in a mouse mutant with an inactivated Purkinje cell-specific gene, Pcp2(L7), that encodes a GoLoco domain-containing modulator of Gi/o protein-coupled receptors. Effects included elevated learning asymptote with repeated rotarod training, increased acquisition rate in tone-cued fear conditioning (FC), and subtle male-specific changes in both acoustic startle habituation and pre-pulse inhibition. We have further analyzed this mutant strain this time with a focus on male-female differences, and here we report a sex-dependent anxiety-like phenotype: male mutants are less anxious, and female mutants are more anxious, than same-sex wild types. Similarly, the fear responses measured during the tone in FC acquisition are decreased in male mutants and increased in female mutants relative to same-sex wild types. Overall, the dynamics of both acquisition and extinction of FC is affected in mutants but memory was not affected. In the social realm, compositional analysis of sociability and preference for social novelty data supports that both L7 genotype and sex contribute to these behaviors. These results provide direct evidence of emotional functions of the cerebellum due to the unambiguous cerebellar specificity of Pcp2(L7) expression and the lack of any confounding motor defects in the mutant. We attempt to synthesize these new data with what is previously known both about Pcp2(L7) and about the effects of sex and sex hormones on anxiety and fear behaviors: specifically, L7 is a bidirectional and sex-dependent damper that regulates the amplitude and/or rate of sensorimotor responses, potentially acting as a mood stabilizer.
James C Walton; Karl Schilling; Randy J Nelson; John Oberdick
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-12
Journal Detail:
Title:  Cerebellum (London, England)     Volume:  -     ISSN:  1473-4230     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101089443     Medline TA:  Cerebellum     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
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