Effects Of Basal Forebrain Lesions Research Articles

Environmental enrichment mitigates the effects of basal forebrain lesions on cognitive flexibility

The aim of the present study was to investigate whether basal forebrain lesions were able to impair a task requiring cognitive flexibility abilities and analyzing the effect of the rearing in an enriched environment on such form of flexibility in rats with or without basal forebrain cholinergic lesions. In adult rats reared in enriched or standard conditions of the cholinergic projection to the neocortex damage was inflicted by 192 IgG-saporin injection into Ch4 region of basal forebrain. Their performance was compared with those of intact animals reared in analogous conditions in a four-choice serial learning task which taps flexibility in adapting to changing response rules. The results underlined the crucial role of the basal forebrain in mediating cognitive flexibility behaviors and revealed that the increase in social interactions, cognitive stimulation and physical activity of the rearing in enriched environment attenuated impairments caused by the cholinergic lesion. These findings demonstrate that rearing in an enriched environment can improve the ability to cope with brain damage suffered in adulthood.

Basal Forebrain Cholinergic Input Is Not Essential for Lesion-Induced Plasticity in Mature Auditory Cortex

The putative role of the basal forebrain cholinergic system in mediating lesion-induced plasticity in topographic cortical representations was investigated. Cholinergic immunolesions were combined with unilateral restricted cochlear lesions in adult cats, demonstrating the consequence of cholinergic depletion on lesion-induced plasticity in primary auditory cortex (AI). Immunolesions almost eliminated the cholinergic input to AI, while cochlear lesions produced broad high-frequency hearing losses. The results demonstrate that the near elimination of cholinergic input does not disrupt reorganization of the tonotopic representation of the lesioned (contralateral) cochlea in AI and does not affect the normal representation of the unlesioned (ipsilateral) cochlea. It is concluded that cholinergic basal forebrain input to AI is not essential for the occurrence of lesion-induced plasticity in AI.

Interactions between the effects of basal forebrain lesions and chronic treatment with MDL 26,479 on learning and markers of cholinergic transmission

The effects of ibotenic acid-induced basal forebrain lesions and treatment with the triazole MDL 26,479 on the acquisition of an operant visual conditional discrimination task and on [ 3H]hemicholinium-3 and [ 3H]vesamicol binding were examined. Lesioned animals required more training sessions to acquire the stimulus-response rules of this task. They also showed longer response latencies throughout the experiment. The effects of the treatment with MDL 26,479 (5 mg/kg; i.p. 60 min before each training session) interacted with the effects of the lesion, producing a decrease in the number of sessions required to perform above chance-level in lesioned but not in control animals. MDL 26,479 did not seem to produce immediate performance effects but interacted with the learning process. The lesions destroyed the cell bodies in the area of the substantia innominata, basal nucleus of Meynert, and the globus pallidus. The number of frontocortical cholinergic terminals as primarily indicated by hemicholinium-3 binding was reduced in lesioned animals; however, another measure of cholinergic terminals, vesamicol binding, was unchanged. Behavioral performance of animals correlated significantly with hemicholinium binding in the frontal cortex of the right hemisphere. The fact that the lesion delayed but did not block the acquisition of the task may have been a result of compensatory mechanisms in remaining cholinergic terminals as indicated by stable vesamicol binding. These data allow assumptions about the conditions for the demonstration of beneficial behavioral effects of MDL 26,479. They also suggest that the long-term effects of basal forebrain lesions on cortical cholinergic transmission remain unsettled.

Long-term effects of basal forebrain lesions on cholinergic, noradrenergic and serotonergic markers in mouse neocortex

Lesions of basal forebrain cholinergic neurons projecting to cerebral cortex and hippocampus have recently been exploited as animal models for some of the neurochemical and behavioral deficits of Alzheimer's disease. We have observed that electrolytic lesions of cholinergic basal forebrain nuclei can lead to morphological plasticity in adult mouse cortex. In the present study, the acute and chronic sequelae of basal forebrain electrolytic lesion on cortical synaptic chemistry have been examined. In addition to choline acetyltransferase (ChAT) activity, levels of norepinephrine and of serotonin were reduced within a week after the lesion. Recovery of ChAT activity and of serotonin levels began within a month after the lesion. Serotonin type 2 receptor binding exhibited an acute reduction after the lesion in ipsilateral cortex, followed later by a chronic bilateral decrease. No significant changes in beta-adrenergic receptors were apparent at any time after the lesion despite a permanent and bilateral reduction of norepinephrine levels after the lesion. The potential significance of these results for cortical plasticity regulation and Alzheimer's disease is discussed.

Sleep suppression following kainic acid-induced lesions of the basal forebrain

We have described elsewhere neurons in the ventral basal forebrain of cats that have elevated discharge rates during sleep and during transitions from waking to sleep, yet have comparatively low discharge rates during waking. These sleep-active neurons may mediate the hypnogenic properties of the basal forebrain. To further evaluate their role in the control of sleep, we examined the effects of basal forebrain lesions produced by microinjections of the relatively cell-selective neurotoxin, kainic acid, on sleep. Lesions were made bilaterally in two regions that contain high densities of sleep-active neurons: the horizontal limb of the diagonal bands of Broca and the lateral preoptic area-substantia innominata. Twelve-hour polygraph recordings were made before and at various intervals after basal forebrain damage in a total of eight cats. The lesions resulted in reduced time spent in deep, nonrapid eye-movement sleep and REM sleep, and increased time spent awake. These abnormalities persisted through 6 to 7 weeks postlesion. Reductions in deep non-REM sleep were due to decreases in bout number, particularly in the number of extended deep non-REM episodes (i.e., those >5 min in duration). The number of REM sleep episodes was also significantly reduced. The average duration of epochs of waking was elevated throughout the postlesion period. Thus, in the postlesion period, cats exhibited an impaired ability to initiate and maintain consolidated periods of sleep, particularly of deeper sleep stages. Lesions were also associated with reduced EEG spindling during sleep. These results are consistent with our hypothesis that sleep-active neurons are a component of a basal forebrain sleep- and EEG-regulating mechanism.

Cholinergic limbic projections and behavioral role of basal forebrain nuclei in the rat

BRAIN RES BULL 16(4) 477–482, 1986.—The purposes of the present study were to identify Cholinergic nonneocortical projections of the basal forebrain and to determine the role of this region in the regulation of estrogendependent reproductive behaviors in the rat. Bilateral electrolytic lesions were placed in an area encompassing the horizontal limb of the diagonal band, as well as portions of the substantia innominata and magnocellular preoptic nucleus, and choline acetyltransferase (CAT) activity was assayed in microdissected brain areas seven days after lesion. Compared to sham surgery, lesions of this region significantly reduced CAT activity in the basal amygdala (34%), dorsal hippocampus (14%), cingulate cortex (25%), piriform cortex (36%), and entorhinal cortex (34%). Other limbic and midbrain structures do not appear to receive significant Cholinergic innervation from this locus since no reductions in CAT were detected after bilateral lesions. These included the anterior hypothalamus, ventromedial hypothalamus, mammillary nucleus, habenula, subiculum, ventral hippocampus, insular cortex, central gray, and interpeduncular nucleus. Behaviorally, female rats with bilateral lesions of the basal forebrain displayed an unusually high incidence of rejection behavior in response to attempted mounts by stimulus male rats in sexual behavior tests. There was no effect of basal forebrain lesions on the incidence of lordosis exhibited by these females. The dissociation of rejection and lordosis suggests that distinct neural pathways mediate the occurrence of these reproductive behaviors and that rejection behavior may be regulated by basal forebrain pathways.

Changes in locomotor activity following basal forebrain lesions in the pigeon

Adult male pigeons (Columba livia) were used to study the effects of basal forebrain lesions upon a measure of responsiveness to the environment, locomotor activity. Daily activity as well as food and water intake and body weight were recorded for Ss through various experimental test phases. Significant reductions occurred in activity scores of all but one experimental S following lesioning, with no changes occurring in controls during comparable test periods. Intrasession analyses of activity showed a tendency for lesion-produced activity depression to affect initial period scores most severely. Small lesions were identified in the parolfactory lobe and paleostriatum or anterior (ventral) thalamic and hypothalamic areas. A possible neuroanatomical explanation for these results was discussed.