Alterations in brain development can result in neurodevelopmental disorders that persistently affect cognitive functions. Common causes of neurodevelopmental disorders in humans include birth complications, environmental factors, or genetic disorders. For instance, genetic channelopathies caused by mutations in ion channels such as SCN2A or KCNQ2 may cause epileptic encephalopathies, both in humans and mice. We have shown that Kv7/M-current-deficient mice exhibit pathological changes in behavior and only develop an epilepsy phenotype when functional M-currents are suppressed during a key neonatal developmental period. Data from animal models and humans suggest that early neuronal activity patterns play an important role in neuronal circuit formation and in the establishment of functional connections between different brain areas. To be able to follow the process of functional maturation of connectivity in the mouse brain, we aim at developing a digital, custom-chip-based recording electrode array using advanced CMOS technology for chronic recordings from freely moving mouse pups and adult mice. This technology will allow us to longitudinally characterize the temporal maturation of cortical and hippocampal network activities and their functional connectivity in wild-type and transgenic mice.
The digital recording array will be used in combination with optogenetic stimulation/inhibition of GABAergig interneurons to characterize the dynamics of network interaction between brain areas and its changes in channelopathy mouse models.
This project is thus devised to provide longitudinal data for the analysis of circuit dynamics of electrical brain development in mouse mutants, resulting in a better understanding of the causal link between early network patterns and a delay or impairment in neurobehavioral development.