Journal of Neuroscience, Vol 14, 2009-2019, Copyright © 1994 by Society for Neuroscience
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
HM Marston, HL West, LS Wilkinson, BJ Everitt and TW Robbins
Department of Experimental Psychology, University of Cambridge, United Kingdom.
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.