title: The brain-derived neurotrophic factor receptor TrkB is critical for the acquisition but not expression of conditioned incentive value.
abstract: Stimuli paired with reward acquire incentive properties that are important for many aspects of motivated behavior, such as feeding and drug-seeking. Here we used a novel chemical-genetic strategy to determine the role of the brain-derived neurotrophic factor (BDNF) receptor TrkB, known to be critical to many aspects of neural development and plasticity, during acquisition and expression of positive incentive value by a cue paired with food. We assessed that cue's learned incentive value in a conditioned reinforcement task, in which its ability to reinforce instrumental responding later, in the absence of food itself, was examined. In TrkB (F616A) knock-in mice, TrkB kinase activity was suppressed by administering the TrkB inhibitor 1NMPP1 during the period of initial cue incentive learning only (i.e. Pavlovian training), during nose-poke conditioned reinforcement testing only, during both phases, or during neither phase. All mice acquired cue-food associations as indexed by approach responses. However, TrkB (F616A) mice that received 1NMPP1 during initial cue incentive learning failed to show conditioned reinforcement of nose-poking, regardless of their treatment in testing, whereas administration of 1NMMP1 only during the testing phase had no effect. The effects of 1NMPP1 administration were due to inhibition of TrkB(F616A), because the performance of wild-type mice was unaffected by administration of the compound during either phase. These data indicate that BDNF or NT4 signaling through TrkB receptors is required for the acquisition of positive incentive value, but is not needed for the expression of previously acquired incentive value in the reinforcement of instrumental behavior.
authors.affiliation: Department of Psychological and Brain Sciences, Neurogenetics and Behavior Center, Johns Hopkins University, Baltimore, MD 21218, USA. awj@jhu.edu
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Johnson
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Hans S
authors.initials: HS
authors.lastname: Crombag
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Dani R
authors.initials: DR
authors.lastname: Smith
authors.forename: Kevan M
authors.initials: KM
authors.lastname: Shokat
authors.forename: Michela
authors.initials: M
authors.lastname: Gallagher
authors.forename: Peter C
authors.initials: PC
authors.lastname: Holland
authors.forename: David D
authors.initials: DD
authors.lastname: Ginty
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009042:Motivation; D009414:Nerve Growth Factors / Q000378:metabolism; D009483:Neuropsychological Tests; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D009414:Nerve Growth Factors; D020813:Receptor, trkB; C073922:neurotrophin 4