Cholinergic Modulation of Visual Attention and Working Memory: Dissociable Effects of Basal Forebrain 192-IgG-saporin Lesions and Intraprefrontal Infusions of Scopolamine

Abstract

Two experiments examined the effects of reductions in cortical cholinergic function on performance of a novel task that allowed for the simultaneous assessment of attention to a visual stimulus and memory for that stimulus over a variable delay within the same test session. In the first experiment, infusions of the muscarinic receptor antagonist scopolamine into the medial prefrontal cortex (mPFC) produced many omissions but did not impair rats' ability to correctly detect a brief visual stimulus. However, these animals were highly impaired in remembering the location of that stimulus following a delay period, although in a delay-independent manner. In the second experiment, another group of animals with selective 192 IgG-saporin lesions of the nucleus basalis magnocellularis (nBM) were not impaired under conditions of low-attentional demand. However, when the stimulus duration was reduced, a significant memory impairment was observed, but similar to the results of the first experiment, the nBM-lesioned animals were not impaired in attentional accuracy, although aspects of attention were compromised (e.g., omissions). These findings demonstrate that (1) cortical cholinergic depletion produces dissociable deficits in attention and memory, depending on the task demands, (2) delay-independent mnemonic deficits produced by scopolamine are probably due to impairments other than simple inattention, and (3) working memory deficits are not simply dependent on attentional difficulties per se. Together, these findings implicate the nBM cortical cholinergic system in both attentional and mnemonic processing.

Disconnection of the amygdala central nucleus and the substantia innominata/nucleus basalis magnocellularis disrupts performance in a sustained attention task.

“…Similarly, Chudasama et al (2004) found no effect on response accuracy when cue duration was reduced from 1 s to 250 ms (although they did see a threefold increase, relative to controls, in the number of trials on which lesioned rats failed to respond, which might also indicate impairment in detecting or attending to those cues). Thus, the role of SI/ nBM itself in this task is still unclear.…”

Alpha-2 Adrenoceptor Activation Inhibits Phencyclidine-Induced Deficits of Spatial Working Memory in Rats

“…The inter-trial interval was 5 s, and the task ended after 125 trials were completed or 60 min passed, whichever came first. The task utilized here is operationally similar to a recent task described by Chudasama and Robbins (Chudasama et al, 2004;Chudasama and Robbins, 2004a), with the exception that their task uses shorter stimulus durations (to tax attentional processes) and involves a match contingency.…”

Combined Damage to Entorhinal Cortex and Cholinergic Basal Forebrain Neurons, Two Early Neurodegenerative Features Accompanying Alzheimer's Disease: Effects on Locomotor Activity and Memory Functions in Rats

“…Second, rats given selective cholinergic lesions in the NBM were not found to exhibit clear deficits in water-maze (Galani et al, 2002) and radial-maze tasks (Galani et al, 2002;Lehmann et al, 2003). Third, Chudasama et al (2004) showed that following injections of 192 IgG-saporin into the NBM, trained rats performed normally under conditions of low-and even high-attentional demands in a combined attention-memory task, but were impaired when tested for memory of the stimulus location. Previously, Risbrough et al (2002) reported similar conclusions on attention after submaximal cholinergic lesions in the NBM.…”