title: Effects of excitotoxic lesions of the septum and vertical limb nucleus of the diagonal band of Broca on conditional visual discrimination: relationship between performance and choline acetyltransferase activity in the cingulate cortex.
abstract: Four experiments examined the role of the cholinergic projections from the septum and vertical limb nucleus of the diagonal band of Broca (VDB) in acquisition and performance of a conditional visual discrimination. In experiments 1-3, excitotoxic lesions were made of the septum and VDB in rats using quisqualic acid, which resulted in significant reductions in ChAT activity in the hippocampus and cingulate cortex, but with no effects on cortical monoamines. In experiment 1, there were significant impairments in acquisition of the conditional discrimination, which did not result from motivational impairments. Experiment 2 repeated these results with lesion parameters, which produced variable effects on hippocampal and cingulate ChAT activity. Those rats with reductions in predominantly cingulate ChAT were most impaired in acquisition, but those with predominantly hippocampal reductions were relatively unimpaired. Experiment 3 showed that quisquate-induced lesions of the VDB, but not of the more caudal VDB and horizontal limb nucleus of the diagonal band, produced deficits, and a model incorporating the results of experiments 1-3 showed a highly significant correlation between errors of commission and cingulate cortical ChAT activity (r = -0.82, p < 0.001). Experiment 4 used the excitotoxin AMPA to lesion the VDB in rats pretrained on a modified form of the conditional discrimination task. In one subgroup of rats this excitotoxin produced profound and regionally selective reductions in ChAT activity. This subgroup was also impaired in relearning the discrimination to criterion. Again, there was a significant inverse relationship between the number of errors of commission made in relearning the discrimination and cingulate ChAT activity (r = -0.94, p < 0.001). These experiments suggest that excitotoxic lesions of the septum/VDB produce deficits in conditional discrimination learning and performance, and that the integrity of the projection to the cingulate cortex is more crucial than that to the hippocampus in this effect. Moreover, there is a close relationship between discrimination performance and cholinergic function in the cingulate cortex. In conjunction with other results, these data suggest that different aspects of cognition and memory are modulated by cholinergic activity in different cortical regions.
authors.affiliation: Department of Experimental Psychology, University of Cambridge, United Kingdom.
authors.forename: H M
authors.initials: HM
authors.lastname: Marston
authors.forename: H L
authors.initials: HL
authors.lastname: West
authors.forename: L S
authors.initials: LS
authors.lastname: Wilkinson
authors.forename: B J
authors.initials: BJ
authors.lastname: Everitt
authors.forename: T W
authors.initials: TW
authors.lastname: Robbins
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003216:Conditioning, Operant / Q000502:physiology*; D004192:Discrimination, Psychological; D004298:Dopamine / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D006179:Gyrus Cinguli / Q000201:enzymology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016318:Quisqualic Acid / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism; D013238:Stereotaxic Techniques; D014796:Visual Perception; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity*
chemical_list: D001679:Biogenic Amines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D002795:Choline O-Acetyltransferase; D004298:Dopamine; D009638:Norepinephrine