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Publication : A molecular dissociation between cued and contextual appetitive learning.

First Author  Kheirbek MA Year  2010
Journal  Learn Mem Volume  17
Issue  3 Pages  148-54
PubMed ID  20189959 Mgi Jnum  J:185848
Mgi Id  MGI:5430287 Doi  10.1101/lm.1687310
Citation  Kheirbek MA, et al. (2010) A molecular dissociation between cued and contextual appetitive learning. Learn Mem 17(3):148-54
abstractText  In appetitive Pavlovian learning, animals learn to associate discrete cues or environmental contexts with rewarding outcomes, and these cues and/or contexts can potentiate an ongoing instrumental response for reward. Although anatomical substrates underlying cued and contextual learning have been proposed, it remains unknown whether specific molecular signaling pathways within the striatum underlie one form of learning or the other. Here, we show that while the striatum-enriched isoform of adenylyl cyclase (AC5) is required for cued appetitive Pavlovian learning, it is not required for contextual appetitive learning. Mice lacking AC5 (AC5KO) could not learn an appetitive Pavlovian learning task in which a discrete signal light predicted reward delivery, yet they could form associations between context and either natural or drug reward, which could in turn elicit Pavlovian approach behavior. However, unlike wild-type (WT) mice, AC5KO mice could not use these Pavlovian conditioned stimuli to potentiate ongoing instrumental behavior in a Pavlovian-to-instrumental transfer paradigm. These data suggest that AC5 is specifically required for learning associations between discrete cues and outcomes in which the temporal relationship between conditioned stimulus (CS) and unconditioned stimulus (US) is essential, while alternative signaling mechanisms may underlie the formation of associations between context and reward. In addition, loss of AC5 compromises the ability of both contextual and discrete cues to modulate instrumental behavior.
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