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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