Document Detail

Sex-dependent behavioral functions of the Purkinje cell-specific Gαi/o binding protein, Pcp2(L7).
MedLine Citation:
PMID:  22528962     Owner:  NLM     Status:  MEDLINE    
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; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cerebellum (London, England)     Volume:  11     ISSN:  1473-4230     ISO Abbreviation:  Cerebellum     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-15     Completed Date:  2013-04-24     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  101089443     Medline TA:  Cerebellum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  982-1001     Citation Subset:  IM    
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MeSH Terms
Anxiety / metabolism
Behavior, Animal* / physiology
Cerebellum / metabolism*
Fear / physiology
Guanine Nucleotide Exchange Factors / genetics,  metabolism*
Learning / physiology
Memory / physiology
Mice, Inbred C57BL
Mutation / genetics
Neuropeptides / genetics,  metabolism*
Purkinje Cells / metabolism*
Sex Characteristics
Grant Support
Reg. No./Substance:
0/Guanine Nucleotide Exchange Factors; 0/Neuropeptides; 0/Pcp2 protein, mouse

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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