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Volume 17, Number 13, Issue of July 1, 1997 pp. 5230-5236
Copyright ©1997 Society for Neuroscience

Disruption of Decrements in Conditioned Stimulus Processing by Selective Removal of Hippocampal Cholinergic Input

Received Jan. 30, 1997; revised April 14, 1997; accepted April 16, 1997.

Mark G. Baxter1, Peter C. Holland3, and Michela Gallagher2

1 Curriculum in Neurobiology and 2 Department of Psychology, University of North Carolina, Chapel Hill, North Carolina 27599, and 3 Department of Psychology: Experimental, Duke University, Durham, North Carolina 27708

The attention directed to environmental stimuli can be modified by experience. For example, preexposure of a conditioned stimulus (CS) in the absence of reinforcement can retard subsequent conditioning of that stimulus when it is paired directly with an unconditioned stimulus, a phenomenon referred to as latent inhibition. Similarly, consistent pairings of a CS with another event can slow the acquisition of new information about that CS. Such phenomena suggest that reductions in the processing of CSs occur when they are made behaviorally irrelevant or consistent predictors of other events. On the basis of the observation that hippocampal lesions prevented such reductions in CS processing, we hypothesized that damage to basal forebrain cholinergic neurons that project to the hippocampus, using microinjections of the selective immunotoxin 192 IgG-saporin into the medial septum/vertical limb of the diagonal band (MS/VDB), also would disrupt normal reductions in CS processing. Lesions of hippocampal cholinergic input disrupted decreases in CS processing, manifested in both an absence of latent inhibition and a lack of reduced processing of a CS that had been a consistent predictor of another CS. These results indicate that cholinergic neurons in the MS/VDB play a role in the regulation of CS processing. Furthermore, these findings (in conjunction with previous findings) implicate both rostral (hippocampal-projecting) and caudal (cortical-projecting) regions of the basal forebrain cholinergic system in the modulation of attention.

Key words: medial septum; acetylcholine; cholinergic basal forebrain; 192 IgG-saporin; immunotoxin; classical conditioning; attention; associative learning; latent inhibition; Alzheimer's disease




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