Molecular and cellular mechanisms of defective neural network rhythm generation

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In this project, we mainly tried to analyze network mechanisms in the hippocampus, thalamus, cerebral cortex and cerebellar cortex, which underlie neurological symptoms such as epilepsy and cerebellar ataxia, using spontaneous mutant neurological mice.We identified a defect in the feedforward circuit of the thalamocortical projection in epileptic calcium channel mutant mice 'tottering'. We demonstrated the defect of synaptic transmission appears in a development-dependent manner. We tried to detect epileptiform discharges using a multi-electrode extracellular recording system, but we failed to obtain stable and consistent results.Until recently, patch clamp recordings from brain slice preparations are mostly from single neurons. Because it is difficult to understand activity of the local network, we started to double- and triple-patch clamp recordings. With this advanced system, we elucidated the basic neural wiring pattern that is required for synchronized activity of thalamic neurons (manuscript in preparation).We were also interested in the morphological impacts of calcium channel mutations. We used retrograde labeling of Purkinje neurons, and developed analysis software to quantitatively measure the territory and branching of Purkinje cell dendritic arbors. In addition to in vitro brain slice recordings, it is essential to record neural activity in vivo. We developed a system for in vivo recording. We are now making comparison between normal and mutant mice.