Deletion of Rapgef6, a candidate schizophrenia susceptibility gene, disrupts amygdala function in mice

• DOI: 10.1038/tp.2015.75
• Publication Date: 2015-06-09T14:13:15Z
• Authors: R J Levy; M Kvajo; Y Li; E Tsvetkov; W Dong; Y Yoshikawa; T Kataoka; V Y Bolshakov; M Karayiorgou; J A Gogos
• Keywords: 0301 basic medicine; 570; 572; DNA Copy Number Variations; Dendritic Spines; Long-Term Potentiation; 610; Prefrontal Cortex; Anxiety; Hippocampus; Mice; 03 medical and health sciences; Conditioning, Psychological; Humans; Animals; Guanine Nucleotide Exchange Factors; Phosphorylation; Spatial Memory; Mice, Knockout; 0303 health sciences; Pyramidal Cells; Fear; Amygdala; CA3 Region, Hippocampal; 3. Good health; Memory, Short-Term; Rapgef6; Schizophrenia; Original Article; Proto-Oncogene Proteins c-fos

Abstract In human genetic studies of schizophrenia, we uncovered copy-number variants in RAPGEF6 and RAPGEF2 genes. To discern the effects deletion humans, investigated behavior neural functions a mouse lacking Rapgef6 . resulted impaired amygdala function measured as reduced fear conditioning anxiolysis. Hippocampal-dependent spatial memory prefrontal cortex-dependent working tasks were intact. Neural activation by cFOS phosphorylation demonstrated reduction hippocampal after conditioning, while morphology assessment spine density primary dendrite number pyramidal neurons CA3 region knockout mice. Electrophysiological analysis showed enhanced long-term potentiation at cortico–amygdala synapses. mice most amygdalar function, brain regions implicated schizophrenia pathophysiology. The results provide deeper understanding role suggest that may be novel therapeutic target schizophrenia.