A necessary role for GluR1 serine 831 phosphorylation in appetitive incentive learning

Hans S. Crombag, Jeffrey M. Sutton, Kogo Takamiya, Hey Kyoung Lee, Peter C. Holland, Michela Gallagher, Richard L. Huganir

Research output: Contribution to journalArticlepeer-review


It is widely thought that regulation of post-synaptic AMPA receptors is a critical component in changes in synaptic efficacy underlying learning and memory. The regulation of AMPA receptors occurs through trafficking of the receptor and/or modulation of the receptor's channel properties and both of these processes depend on phosphorylation of the receptor. Using homologous recombination (knock-in) techniques we targeted two phosphorylation sites on the AMPA-GluR1 receptor: the CaMKII/PKC Ser 831 site and the PKA Ser 845 site. Mice with either or both of these sites mutated were then tested on an incentive learning task that assessed their ability to acquire a simple association between a cue and reward and to then use this cue as a reinforcer to guide their behavior (conditioned reinforcement). We report that, whereas WT mice showed enhanced responding for the reward-associated cue, mice with mutations of both phosphorylation sites or the Ser 831 site alone, failed to show such a conditioned reinforcement effect. By contrast, mice with only the Ser 845 site deficient showed normal CS+ reinforced responding. Thus, action at the Ser 831 phosphorylation site was necessary for normal conditioned reinforcement. Finally, the behavioral deficit was highly specific: performance on a number of other measures of motivated performance, including responding reinforced by the food itself, was unaffected by the mutations. Our findings provide novel evidence for a molecular mechanism in a form of appetitive incentive learning critical in regulating normal motivated behavior, as well as maladaptive forms such as addiction and eating disorders.

Original languageEnglish (US)
Pages (from-to)178-183
Number of pages6
JournalBehavioural Brain Research
Issue number2
StatePublished - Aug 22 2008


  • Conditioned reinforcement
  • Glutamate
  • Synaptic plasticity
  • Transgenic mice

ASJC Scopus subject areas

  • Behavioral Neuroscience

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