Evidence for altered hippocampal function in a mouse model of the human 22q11.2 microdeletion

摘要: 22q11.2 chromosomal deletions are recurrent copy number mutations that increase the risk of schizophrenia around thirty-fold. Deletion orthologous region in mice offers an opportunity to characterize changes neuronal structure and function may account for development this disease. The hippocampus has been implicated pathogenesis, is reduced volume deletion carriers displays altered a mouse model mutation (Df(16)A(+/-) mice). Here we investigate hippocampal CA1 physiology, hippocampal-dependent spatial memory novelty-induced activation Df(16)A(+/-) mice. We found normal reference (as assayed by Morris water maze test) as well modest but potentially important deficits physiology. In particular, reduction level inhibition pyramidal neurons was observed, implying decrease interneuron activity. Additionally, LTP were observed using certain induction protocols. Induction c-Fos expression exploration novel environment suggested relative sparing dentate gyrus showed robust activated CA3 Overall, experiments performed demonstrated various degrees across different regions hippocampus, which together contribute increased developing schizophrenia.