THE CEREBRAL METABOLIC EFFECTS OF MANIPULATING GLUTAMATERGIC SYSTEMS WITHIN THE BASAL FOREBRAIN IN CONSCIOUS RATS

N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated manipulatio ns of the cortical cholinergic input arising from the basal forebrain differentially affect cognitive function. We used [C-14]-2-deoxyglucos e autoradiography in conscious rats to map the effects of excitatory a mino acid agonist infusions into the nucleus basalis magnocellularis ( NBM) on cerebral functional activity, as reflected by local rates of g lucose utilization. Acute stimulation of NBM neurones by local infusio n of lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), 1 5 min before glucose use measurement, resulted in glucose use reductio ns in nine cortical regions innervated by NBM efferents including pref rontal, frontal, sensorimotor and cingulate cortices. NMDA infusions a ltered glucose use in two cortical areas. Both AMPA and NMDA markedly increased glucose use in the striatum and globus pallidus, with concom itant perturbations in striato-pallidal projection targets including t he substantia nigra, entopeduncular nucleus, subthalamic nucleus and l ateral habenular nucleus. In contrast, the GABA(A) agonist muscimol di d not affect glucose use in the NBM or neocortical regions, but induce d glucose use increases in several subcortical nuclei including the su bstantia nigra and entopeduncular nucleus, The delayed effects of exci totoxic lesions were assessed 3 weeks after basal forebrain infusions of AMPA, NMDA, ibotenate or quisqualate. Statistically significant glu cose use changes only occurred in the hypothalamus after NMDA, and the NBM after ibotenate infusions, although reduced cortical metabolism w as apparent following AMPA-induced lesions of the NBM. Results support a dissociation between the functional sequelae of NMDA and non-NMDA r eceptor-mediated events in the basal forebrain, and long-term compensa tory functional adaptation following cortical denervation.