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The Journal of Neuroscience, October 29, 2008, 28(44):11401-11408; doi:10.1523/JNEUROSCI.4115-08.2008

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Behavioral/Systems/Cognitive
A cAMP Pathway Underlying Reward Prediction in Associative Learning

Mazen A. Kheirbek,¹ Jeff A. Beeler,² Yoshihiro Ishikawa,³ and Xiaoxi Zhuang²

¹Committee on Neurobiology and ²Department of Neurobiology, The University of Chicago, Chicago, Illinois 60637, and ³Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Newark, New Jersey 07103

Correspondence should be addressed to Xiaoxi Zhuang, Department of Neurobiology, The University of Chicago, 924 East 57th Street, Knapp R214, Chicago, IL 60637. Email: xzhuang{at}bsd.uchicago.edu

In associative learning, animals learn to associate external cues or their own actions with appetitive or aversive outcomes. Although the dopamine (DA) system and the striatum/nucleus accumbens have been implicated in both the pavlovian and instrumental form of associative learning, whether specific neuronal signaling mechanisms underlie one form or the other is unknown. Here, we report that the striatum-enriched isoform of adenylyl cyclase (AC), AC5, is selectively required for appetitive pavlovian learning. Mice with genetic deletion of AC5 (AC5KO) acquired instrumental responding yet were unable to use cues that predicted reward delivery. The specificity of this deficit was confirmed by an inability of AC5KO mice to learn a simple appetitive pavlovian conditioning task. Conversely, AC5KO mice showed intact aversive pavlovian learning, suggesting the deficit was specific for learning about appetitive outcomes. Our results suggest that AC5 is a critical component of DA-dependent strengthening of stimulus–reward contingencies.

Key words: pavlovian conditioning; dopamine; instrumental conditioning; striatum; adenylyl cyclase; reward prediction

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Received Aug. 28, 2008; accepted Sept. 23, 2008.

Correspondence should be addressed to Xiaoxi Zhuang, Department of Neurobiology, The University of Chicago, 924 East 57th Street, Knapp R214, Chicago, IL 60637. Email: xzhuang{at}bsd.uchicago.edu

This article has been cited by other articles:

				M. A. Kheirbek, J. P. Britt, J. A. Beeler, Y. Ishikawa, D. S. McGehee, and X. Zhuang Adenylyl Cyclase Type 5 Contributes to Corticostriatal Plasticity and Striatum-Dependent Learning J. Neurosci., September 30, 2009; 29(39): 12115 - 12124. [Abstract] [Full Text] [PDF]

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