title: A molecular dissociation between cued and contextual appetitive learning.
abstract: 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.
authors.affiliation: Committee on Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA. mk3156@columbia.edu
authors.forename: Mazen A
authors.initials: MA
authors.lastname: Kheirbek
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Beeler
authors.forename: Wanhao
authors.initials: W
authors.lastname: Chi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhuang
mesh_terms: D000262:Adenylyl Cyclases / Q000172:deficiency / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001070:Appetitive Behavior / Q000502:physiology*; D001245:Association Learning / Q000502:physiology*; D003042:Cocaine / Q000008:administration & dosage; D003214:Conditioning, Classical / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000293:injuries / Q000502:physiology*; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D007527:Isoenzymes / Q000172:deficiency / Q000378:metabolism; D007859:Learning Disabilities / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D014163:Transfer, Psychology / Q000187:drug effects / Q000502:physiology
chemical_list: D018765:Dopamine Uptake Inhibitors; D007527:Isoenzymes; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V; D003042:Cocaine