Removal of cholinergic input to rat posterior parietal cortex disrupts incremental processing of conditioned stimuli

Abstract

Recent research suggests that the basal forebrain cholinergic neurons innervating the cortex play a role in attentional functions in both primates and rodents. Among the cortical targets of these projections in primates is the posterior parietal cortex (PPC), a region shown to be critically involved in the regulation of attention. Recent anatomical studies have defined a cortical region in the rat that may be homologous to the PPC of primates. In the present study, cholinergic innervation of the PPC was depleted by intracortical infusion of the immunotoxin 192 IgG-saporin. Control and lesioned rats were then tested in two associative learning paradigms designed to increase attentional processing of conditioned stimuli (CSs). In one experiment, attention was manipulated by shifting a predictive relation between a light CS and another CS to a less predictive relation. Unlike control rats, lesioned rats failed to increase attention when the predictive relation was modified. In a second experiment, attentional processing of a tone CS was increased when its introduction during training coincided with a change in the value of the unconditioned stimulus, a phenomenon referred to as unblocking. Unlike control rats, lesioned rats failed to exhibit unblocking. In both paradigms, lesioned rats conditioned normally when the training procedures did not encourage increased attentional processing. These findings, across different behavioral paradigms and stimulus modalities, provide converging evidence that intact cholinergic innervation of the PPC is important for changes in attention that can increase the processing of certain cues.

Fig. 1.

Photomicrographs of AChE-stained coronal sections from a vehicle-injected control brain (a) and a PPC-immunolesioned brain (b). Note the decrease in AChE staining in the PPC (located between the arrows) of the immunolesioned brain. In contrast, staining in the cortex located medial to the PPC is comparable in the control and lesioned brains. Also note that the band of darker AChE staining in the intermediate layers of dorsal lateral cortex in the control brain is visible beyond the border of PPC in the lesioned brain.

Fig. 2.

Photomicrographs of stained sections within the PPC of a vehicle-injected control brain (left) and PPC-immunolesioned brain (right). Parvalbumin immunostaining (a, b) was comparable in control and immunolesioned brains (10× magnification). Noncholinergic, myelin-stained fibers (arrows in c, d) in the superficial layers of PPC were intact in both control and immunolesioned brains (40× magnification).

Fig. 3.

Acquisition of food cup behavior to the light CS during the test phase of Experiment 1 (mean ± SEM). Theleft panel shows the performance of control rats; theright panel shows the performance of PPC-immunolesioned rats. Groups for which the predictive validity of the light was shifted in Phase 2 (CTL-S and PPC-S) are indicated by ○; groups for which the predictive validity of the light remained consistent with that in Phase 1 are indicated by •.

Fig. 4.

Conditioned responding to the tone during the test phase of Experiment 2 (mean + SEM). Groups for which the value of the US was downshifted from high to low in Phase 2 (CTL-Dn and PPC-Dn) are indicated by the empty bars; groups for which the value of the US remained low throughout Phases 1 and 2 are indicated by thefilled bars.