Electrical excitability is a basic characteristic of the vertebrate CNS and an integral component to its proper functioning. In the present proposal, several important questions relating to the electrical excitability of mammalian CNS neurons will be addressed, with the intent of obtaining information basic to an understanding of CNS neuronal function at the cellular, membrane and molecular levels. The immediate goals of the proposed research are to define the ionic mechanisms responsible for neuronal excitability in an identified mammalian CNS neuron, to establish if these mechanisms are segregated in the somal vs dendritic region of the neuron and to detail the developmental sequence of these characteristics during the maturation process. The Purkinje neuron (PN) of the cerebellum was selected for study because of its unique suitability for the proposed studies and because there are compelling reasons to believe that the information obtained from PNs can be directly extended to several other CNS neuronal types which display analogous electrical events. In order to achieve the stated goals, a tissue culture preparation will be used which offers considerable technical and anatomical advantage. Initial studies demonstrated the validity of the model for the proposed studies. Generally accepted experimental approaches will be used including 3 types of electropysiological recordings (extracellular, intracellular, single channel), manipulation of the intracellular and extracellular ionic environments and application of ion channel blockers which demonstrate specificity for particular ion channels. This approach will provide in-depth information on the physiology of the mammalian CNS neurons both in the mature state and at various developmental stages during the maturation process. Such information is basic to an understandin of normal CNS neuronal function and alterations or deficiencies in cellular processes which may underlie abnormal brain function.
