The goals of this investigation are to evaluate the intrinsic organization, receptor binding and response properties of neurons in cingulate cortex, one of the major components of the limbic system. Intrinsic organization will be assessed with Golgi and degeneration techniques in the rabbit brain. Rapid Golgi material will provide information about the types of neurons and the intracortical distribution of their axons, particularly for those cells which are unique to limbic cortex including extraverted and fusiform pyramids. The neurotoxin ibotenic acid will be used to assess the density and extent of longer intrinsic connections. Ablations will be made in the superficial or deep layers with this toxin and then light and electron microscopic techniques used to determine where most of the neurons in a particular layer terminate. Muscarinic acetylcholine receptors will be localized to specific types of neurons in the rat by making ablations with ibotenic acid or acetylethycholine mustard followed by evaluation of changes in the density of receptors using an in vitro assay. This assay employs cryostat sectioning of cingulate cortex followed by incubation of the sections in the irreversible muscarinic ligand H3-propylbenzilylcholine mustard. A thorough ultrastructural analysis is also proposed in order to assess exactly what morphological changes underlie the action of excitotoxins. Neuronal responses will be evaluated in area 29d during eye movements. Extracellular recordings from an acute rabbit preparation will be made in conjunction with monitoring eye position with an infrared light emitting diode mounted on a contact lens. The phase relationships between neuronal discharges and the direction duration and amplitude of eye movements will be evaluated. The connectional basis of these responses will be clarified using thalamic ablation and/or cortical cooling techniques in addition to an anatomical tract tracing technique. These projects will lead to a more complete understanding of the cholinergic system and as such will help to interpret alterations in receptor binding patterns that occur in the cingulate cortices of patients with Alzheimer's disease. Finally, before an interpretation and treatment of the movement disorder akinetic mutism can be made, it will be necessary to understand the sensorimotor functions of cingulate cortex.
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