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The Journal of Neuroscience, February 1, 2003, 23(3):1041
Selective Disruption of Stimulus-Reward Learning in Glutamate Receptor gria1 Knock-Out Mice
Andy N. Mead and David N. Stephens Laboratory of Experimental Psychology, University of Sussex, Brighton BN1 9QG, United Kingdom
Glutamatergic neurotransmission via AMPA receptors has been an important focus of studies investigating neuronal plasticity. AMPA receptor glutamate receptor 1 (GluR1) subunits play a critical role in long-term potentiation (LTP). Because LTP is thought to be the cellular substrate for learning, we investigated whether mice lacking the GluR1 subunit [gria1 knock-outs (KO)] were capable of learning a simple cue-reward association, and whether such cues were able to influence motivated behavior. Both gria1 KO and wild-type mice learned to associate a light/tone stimulus with food delivery, as evidenced by their approaching the reward after presentation of the cue. During subsequent testing phases, gria1 KO mice also displayed normal approach to the cue in the absence of the reward (Pavlovian approach) and normal enhanced responding for the reward during cue presentations (Pavlovian to instrumental transfer). However, the cue did not act as a reward for learning a new behavior in the KO mice (conditioned reinforcement). This pattern of behavior is similar to that seen with lesions of the basolateral nucleus of the amygdala (BLA), and correspondingly, gria1 KO mice displayed impaired acquisition of responding under a second-order schedule. Thus, mice lacking the GluR1 receptor displayed a specific deficit in conditioned reward, suggesting that GluR1-containing AMPA receptors are important in the synaptic plasticity in the BLA that underlies conditioned reinforcement. Immunostaining for GluR2/3 subunits revealed changes in GluR2/3 expression in the gria1 KOs in the BLA but not the central nucleus of the amygdala (CA), consistent with the behavioral correlates of BLA but not CA function.
Key words: learning; Pavlovian association; conditioned reinforcement; second order conditioning; Pavlovian to instrumental transfer; Pavlovian approach; AMPA receptor; GluR-A subunit; GluR1 subunit; GluR2 subunit; amygdala
Copyright © 2003 Society for Neuroscience 0270-6474/03/2331041-08$05.00/0
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