| RRC ID |
77814
|
| Author |
Levy RJ, Kvajo M, Li Y, Tsvetkov E, Dong W, Yoshikawa Y, Kataoka T, Bolshakov VY, Karayiorgou M, Gogos JA.
|
| Title |
Deletion of Rapgef6, a candidate schizophrenia susceptibility gene, disrupts amygdala function in mice.
|
| Journal |
Transl Psychiatry
|
| Abstract |
In human genetic studies of schizophrenia, we uncovered copy-number variants in RAPGEF6 and RAPGEF2 genes. To discern the effects of RAPGEF6 deletion in humans, we investigated the behavior and neural functions of a mouse lacking Rapgef6. Rapgef6 deletion resulted in impaired amygdala function measured as reduced fear conditioning and anxiolysis. Hippocampal-dependent spatial memory and prefrontal cortex-dependent working memory tasks were intact. Neural activation measured by cFOS phosphorylation demonstrated a reduction in hippocampal and amygdala activation after fear conditioning, while neural morphology assessment uncovered reduced spine density and primary dendrite number in pyramidal neurons of the CA3 hippocampal region of knockout mice. Electrophysiological analysis showed enhanced long-term potentiation at cortico-amygdala synapses. Rapgef6 deletion mice were most impaired in hippocampal and amygdalar function, brain regions implicated in schizophrenia pathophysiology. The results provide a deeper understanding of the role of the amygdala in schizophrenia and suggest that RAPGEF6 may be a novel therapeutic target in schizophrenia.
|
| Volume |
5(6)
|
| Pages |
e577
|
| Published |
2015-6-9
|
| DOI |
10.1038/tp.2015.75
|
| PII |
tp201575
|
| PMID |
26057047
|
| PMC |
PMC4490285
|
| MeSH |
Amygdala / physiopathology*
Animals
Anxiety / genetics*
CA3 Region, Hippocampal / pathology
Conditioning, Psychological*
DNA Copy Number Variations
Dendritic Spines / pathology*
Fear*
Guanine Nucleotide Exchange Factors / genetics*
Hippocampus / pathology
Hippocampus / physiopathology*
Long-Term Potentiation / genetics
Memory, Short-Term
Mice
Mice, Knockout
Phosphorylation
Prefrontal Cortex / physiopathology
Proto-Oncogene Proteins c-fos / metabolism
Pyramidal Cells / pathology*
Schizophrenia / genetics*
Spatial Memory
|
| IF |
5.28
|
| Resource |
| Mice |
RBRC02699 |
