UMMS Affiliation

Department of Pediatrics; Department of Psychiatry, Brudnick Neuropsychiatric Research Institute

Publication Date


Document Type



Animals; Autoradiography; Cues; DNA, Recombinant; Entorhinal Cortex; Gene Targeting; Learning; Macaca mulatta; Photic Stimulation; Receptors, Dopamine D2; *Reward


Neurology | Pediatrics | Psychiatry


When schedules of several operant trials must be successfully completed to obtain a reward, monkeys quickly learn to adjust their behavioral performance by using visual cues that signal how many trials have been completed and how many remain in the current schedule. Bilateral rhinal (perirhinal and entorhinal) cortex ablations irreversibly prevent this learning. Here, we apply a recombinant DNA technique to investigate the role of dopamine D2 receptor in rhinal cortex for this type of learning. Rhinal cortex was injected with a DNA construct that significantly decreased D2 receptor ligand binding and temporarily produced the same profound learning deficit seen after ablation. However, unlike after ablation, the D2 receptor-targeted, DNA-treated monkeys recovered cue-related learning after 11-19 weeks. Injecting a DNA construct that decreased N-methyl-d-aspartate but not D2 receptor ligand binding did not interfere with learning associations between the cues and the schedules. A second D2 receptor-targeted DNA treatment administered after either recovery from a first D2 receptor-targeted DNA treatment (one monkey), after N-methyl-d-aspartate receptor-targeted DNA treatment (two monkeys), or after a vector control treatment (one monkey) also induced a learning deficit of similar duration. These results suggest that the D2 receptor in primate rhinal cortex is essential for learning to relate the visual cues to the schedules. The specificity of the receptor manipulation reported here suggests that this approach could be generalized in this or other brain pathways to relate molecular mechanisms to cognitive functions.

Rights and Permissions

Copyright © 2004, The National Academy of Sciences. Freely available online through the PNAS open access option.

DOI of Published Version



Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12336-41. Epub 2004 Aug 9. Link to article on publisher's site

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

Related Resources

Link to Article in PubMed

PubMed ID