Cholinergic Projection from the Basal Forebrain and Cerebral Glucose Metabolism in Rats: A Dynamic PET Study

To investigate the influence of cholinergic projections from the basal forebrain on cerebral cortex metabolism, we evaluated the cerebral metabolic rate of glucose (CMRGlu) after selective inhibition of cholinergic neurons in the rat basal forebrain using the pyruvate dehydrogenase complex inhibitor 3-bromopyruvic acid (BPA), and compared the results with those obtained after lesioning the basal forebrain with ibotenic acid, as well as with those from a sham-operated control group. CMRGlu was measured using positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG). Three days after surgery, CMRGlu and k3 (phosphorylation of FDG) were reduced similarly in the frontal cortex on the BPA-injected side and in the ibotenic acid-treated group, whereas K1 (transport rate of FDG from the plasma to brain) showed no marked changes. At 3 weeks postoperatively, the CMRGlu and k3 of the frontal cortex in both groups recovered to levels similar to those of the sham-operated group. The main difference between the BPA and ibotenic acid groups was that CMRGlu showed mild reduction on the side contralateral to the operation in the former, while such reduction was confined to the ipsilateral hemisphere in the latter. The present results indicate that the cholinergic system in the basal forebrain regulates cerebral cortex glucose metabolism through direct excitation of cortical neurons.