The proposed research is designed to obtain a basic understanding of the electrophysiological membrane properties and local synpatic circuitry of cholinergic neurons in the basal forebrain. Since basal forebrain cholinergic systems have been implicated in the etiology of Alzheimer's disease, a knowledge of the cellular physiology of these neurons is essential for the further understanding and eventual treatment of senile dementia. To date, the paucity of electrophysiological data results from the inability to clearly separate and identify cholinergic neurons. The present proposal attempts to overcome these difficulties by the use of the in vitro brain slice preparation, intracellular recording techniques and immunofluorescent labelling methods. As in vitro guinea-pig brain slice will include the nucleus of the diagnal band, nucleus basalis and medial septum. Electrophysiological characteristics of individual cells within these nuclei will then be studied with intracellular recording techniques. To verify the cholinergic nature of the neurons studied, a double-labelling procedure will be used that includes, first, intracellular injection of horseradish peroxidase followed by immunofluorescent staining for the presence of choline acetyltransferase. The combined use of intracellular electrophysiological recording and immunofluorescent staining techniques will enable specific information to be gained regarding the cellular mechanisms of cholinergic neurons in the basal forebrain. This basic knowledge of the microphysiology of these cells will provide a basis for future pharmacological studies attempting to reverse or correct the progressive dementia in Alzheimer's patients.