Differential Role of Muscarinic Transmission within the Entorhinal Cortex and Basolateral Amygdala in the Processing of Irrelevant Stimuli

Cholinergic projections to the entorhinal cortex (EC) and basolateral amygdala (BLA) mediate distinct cognitive processes through muscarinic acetylcholine receptors (mAChRs). In this study, we sought to further differentiate the role of muscarinic transmission in these regions in cognition, using the latent inhibition (LI) phenomenon. LI is a cross-species phenomenon manifested as poorer conditioning to a stimulus experienced as irrelevant during an earlier stage of repeated non-reinforced pre-exposure to that stimulus, and is considered to index the ability to ignore, or to in-attend to, irrelevant stimuli. Given our recent findings that systemic administration of the mAChR antagonist scopolamine can produce two contrasting LI abnormalities in rats, ie, abolish LI under conditions yielding LI in non-treated controls, or produce abnormally persistent LI under conditions preventing its expression in non-treated controls, we tested whether mAChR blockade in the EC and BLA would induce LI abolition and persistence, respectively. We found that intra-EC scopolamine infusion (1, 10 mu g per hemisphere) abolished LI when infused in pre-exposure or both pre-exposure and conditioning, but not in conditioning alone, whereas intra-BLA scopolamine infusion led to persistent LI when infused in conditioning or both stages, but not in pre-exposure alone. Although cholinergic innervation of the EC and BLA has long been implicated in attention to novel stimuli and in processing of motivationally significant stimuli, respectively, our results provide evidence that EC mAChRs also have a role in the development of inattention to stimuli, whereas BLA mAChRs have a role in re-attending to previously irrelevant stimuli that became motivationally relevant. Neuropsychopharmacology (2010) 35, 1073-1082; doi: 10.1038/npp.2009.210; published online 13 January 2010