Altered function and maturation of primary cortical neurons from a 22q11.2 deletion mouse model of schizophrenia.

摘要: Given its high penetrance, clearly delineated and evolutionary conserved genomic structure, mouse models of the 22q11.2 deletion provide an ideal organism-based cell-based model this well-established disease mutation for schizophrenia. In study we examined development changes in intrinsic properties, action potential firing synaptic transmission using whole-cell patch-clamp recordings cultured embryonic cortical neurons from Df(16)A +/- WT mice at DIV7 DIV14, respectively. Compared to littermates, significantly increased input resistance decreased rising rate was observed but not DIV14 indicative delayed neuronal maturation. Neurons also showed higher cellular excitability both DIV14. Evaluation Ca2+ homeostasis perturbation caused by calcium imaging revealed a lower amplitude elevation smaller area under curve after depolarization Furthermore, properties inhibitory events were altered mice. We identified mRNA expression profiles, especially ion channels, receptors, transporters that may underlie neurophysiological effects mutation. Overall, show number alterations electrophysiological homeostatic different culture times valuable insights towards revealing mechanisms discovery new therapeutic compounds.