The goal of this project is to understand how genetic mutations in mice which effect neurological function and are associated with malformation of the cerebellar cortex alter the electrical excitability of identified neurons. Patch clamp methods will be used to record ionic currents from granule and Purkinje cells in cultures of dissociated mouse cerebellum. Experiments will investigate the types and relative numbers of voltage-gated Ca2+ and K+ channels their gating mechanisms, and sensitivity of channel activity to phosphorylation. Information about ion channels in cells from wild-type mice will be used to investigate alterations in neuronal excitability in the weaver and staggerer neurological mutants. Whole-cell and single channel recordings from growth cones in wild-type and weaver granule cells will be made to determine whether the defect in cell motility in the mutant is associated with changes in the types. numbers, activity, or pharmacological sensitivity of voltage-gated Ca2+ and K+ channels. Recordings from the cell body and dendrites of staggerer Purkinje cells in culture will determine whether the absence of Ca2+ action potentials in adult cells in vivo is characteristic of the mutant phenotype in vitro and will investigate the changes in microscopic channel properties underlying the Ca2+ channel deficit. These experiments are important for understanding altered neuronal excitability underlying human neuropsychiatric disease and the mechanisms by which genetic mutations produce developmental neuropathologies during formation of the central nervous system.
| Slesinger, P A; Lansman, J B (1991) Inactivation of calcium currents in granule cells cultured from mouse cerebellum. J Physiol 435:101-21 |
| Slesinger, P A; Lansman, J B (1991) Inactivating and non-inactivating dihydropyridine-sensitive Ca2+ channels in mouse cerebellar granule cells. J Physiol 439:301-23 |
