Brain Research, 279 (1983) 41-52 41 Elsevier Lesions of the Basal Forebrain in Rat Selectively Impair the Cortical Vasodilation Elicited from Cerebellar Fastigial Nucleus COSTANTINO IADECOLA, SIMA MRAOVITCH, MARY P. MEELEY and DONALD J. REIS* Laboratory of Neurobiology, Department of Neurology, Cornell University Medical College, 1300 York Avenue, New York, NY IO021 (U.S.A.) (Accepted March 8th, 1983) Key words: basal forebrain lesions - - fastigial nucleus - - cortical vasodilation We sought to determine in rat, whether interruption of the major extrathalamic projections to the cerebral cortex originating in and projecting through the basal forebrain (BF), will impair the increase in regional cerebral blood flow (rCBF), but not metabolism, elic- ited in the cerebral cortex by electrical stimulation of the cerebellar fastigial nucleus (FN). Studies were conducted in anesthetized, paralyzed, ventilated rats, with blood gases controlled and AP maintained in the autoregulated range. Electrolytic lesions were placed unilaterally in the BF at the level of the lateral preoptic region lying in rostral portions of the medial forebrain bundle and resulted in a reduction of up to 47% of the choline acetyltransferase activity in the ipsilateral cerebral cortex, rCBF was measured in homogenates of 9 paired brain regions by the 14C-iodoantipyrinetechnique. In unlesioned rats, FN stimulation symmetrically and significantly (P < 0.05) increased rCBF in all brain regions with the greatest increase (to 180%) in the frontal cortex. Two days following a unilater- al BF lesion, FN stimulation failed to increase rCBF in the ip_silateral cerebral cortex distal to the BF lesion. In contrast, rCBF was in- creased to an almost comparable degree in the remainder of the brain. BF lesions alone resulted in a 18-23% reduction in cortical rCBF ipsilaterally (P < 0.025). BF lesions did not alter the cerebrovascular vasodilation elicited by CO2 nor perturb autoregulation. The cortical vasodilation elicited by FN stimulation is mediated by intrinsic neuronal pathways and depends upon the integrity of neu- rons, possibly cholinergic, originating in, or passing through, the BF. INTRODUCTION We have recently discovered that in rat, electrical stimulation of the fastigial nucleus (FN) of cerebel- lum will markedly and significantly increase regional cerebral blood flow (rCBF) throughout the brain 22. The magnitude of the changes in rCBF vary among different brain regions but are maximal in the cere- bral cortex where rCBF can be increased 1.5- to 3- fold. Of particular importance is the fact that in the cerebral cortex, the increase of rCBF is unassociated with changes in regional glucose utilization23. This latter finding indicates that fibers originating in or passing through the FN can mediate a primary vaso- dilation in the cerebral cortex23,32, that is, vasodila- tion uncoupled from, and independent of, neuronal metabolism. The increase in rCBF produced in rat and rabbit32 by FN stimulation persists after transection of the spi- nal cord at the first cervical segment by interruption of the cervical sympathetic chain22,23, and by transec- tion of the VIIth cranial nerve23. These observations have led us to propose22, 32 that the evoked vasodila- tion is a consequence of excitation of intrinsic neural pathways synaptically connected to projections origi- nating in, or passing through, the FN and not second- ary to effects mediated via peripheral nerves inner- vating the cerebral vessels, nor to release of vasoac- tive hormones from the periphery. However, FN stimulation could still influence the cerebral circula- tion by release of hormones from hypothalamus or pituitary. Indeed, our recent observation that FN stimulation will release substantial amounts of vaso- pressin5 demonstrates that the FN can exert an im- portant control over neuroendocrine mechanisms. In the present study, therefore, we have sought to determine whether the increase of rCBF in the cere- bral cortex produced by FN stimulation can be abol- * To whom correspondence should be addressed. 0006-8993/83/$03.00 © 1983 Elsevier Science Publishers B.V.