Experiments are proposed to provide a critical assessment of the use of (14C)-2-deoxglucose and specifically labeled (14C)-glucose in the measurement of cerebral functional activity. The uptake and retention of radioactivity in discrete brain regions from (14C)-2-deoxyglucose, (1-14C)-glucose and (6-14C)-glucose will be evaluated with high resolution autoradiography in which 4 um frozen brain sections are thaw-mounted onto nuclear emulsion coated slides. These studies will delineate the similarities and differences in the relative uptake and retention of radioactivity from the various compounds and in glucose utilization rates determined with the appropriate kinetic models. The hypothesis will be tested that the previously demonstrated low retention of radioactivity from (14C)-2-DG in some brain regions relative to that from (1-14C)-glucose is due to regionally high glucose-6- phosphatase activity, low phosphorylation of 2-DG, or low transport of (14C)-2-deoxyglucose-6- phosphate accumulation will be measured in microdissected brain regions by liquid scintillation counting in rats killed by microwave radiation, 1 to 45 minutes after i.v. injection of (14C)-deoxyglucose. If some brain regions contain high glucose-6-phosphate activity, an initial accumulation, followed by a decline in 2-deoxyglucose-6- phosphate, is predicted. If a brain region exhibits low phosphorylation of (14C)-2-DG, little accumulation of (14C)-2-DG is not transported as effectively into the cells of certain regions as is glucose, low levels of accumulation of radioactivity from (14C)-2-DG will occur at all times. The ability of (14C)-2-DG and specifically labelled (14C)-glucose to register alterations in functional activity will be determined by sensory stimulation and by stimulating a well defined afferent pathway to the hippocampal formation. Concurrent electrophysiological recording will be performed to determine the relationship of metabolic and electrical activities.
