Chemogenetic Disruption of Monkey Perirhinal Neurons Projecting to the Rostromedial Caudate Impairs Associative Learning

Abstract

Primates, including humans, use stimulus–reward associations to guide foraging. We previously showed that both the rhinal cortex (Rh) and rostromedial caudate (rmCD) of rhesus monkeys play causal roles in assigning value to visual stimuli. Layer 5 neurons in Rh project to rmCD. Here, we reversibly interrupted this Layer 5 connection in two male monkeys by combining a unilateral Rh lesion with contralateral expression of an inhibitory DREADD delivered using a retrograde lentivirus (fusion glycoprotein type E) injected into rmCD. Interruption of projection neurons from Rh to rmCD had little effect on already learned stimulus–reward associations but impaired the learning of new associations. The learning impairment appeared when the projection neurons from the perirhinal cortex (PRh) to rmCD were silenced using microinjections of deschloroclozapine into PRh. The pathway-specific silencing led to a significant deficit in learning new stimulus–reward associations. These results suggest that the learning, but not retrieval, of visual stimulus–reward associations involves projection neurons from PRh to rmCD.