Disruption of decrements in conditioned stimulus processing by selective removal of hippocampal cholinergic input

Abstract

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.

Fig. 1.

Unconditioned orienting (rearing) to the visual CS during the preexposure phase of Experiment 1. The unconditioned rearing response habituates across sessions of preexposure; this habituation is equivalent in control rats (open squares) and rats with immunolesions of the MS/VDB (filled squares).

Fig. 2.

Acquisition of conditioned responding (food cup behavior) to the preexposed and novel CSs in the conditioning phase of Experiment 1. Control rats (left) develop greater conditioning to the novel CS (open triangles), as compared with the preexposed CS (open squares), indicative of latent inhibition. In contrast, rats with immunolesions of the MS/VDB (right) demonstrate equivalent conditioning to the preexposed (filled squares) and novel (filled triangles) stimuli.

Fig. 3.

Acquisition of conditioned responding (percentage of time in food cup) during the five sessions of phase 3 in Experiment 2. Responding to the light during the final session of phase 2 is included for comparison (P). Control rats (CTL; open symbols) in the Shift condition demonstrate greater conditioning relative to rats in the Consistent condition. In contrast, rats with immunolesions of the MS/VDB (MS/VDB; closed symbols) in the Consistent and Shift conditions show equivalent levels of conditioning, at the level of the CTL-Shift rats.