Rapid strengthening of thalamo-amygdala synapses mediates cue–reward learning

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Abstract
Some people earn rewards more successfully than others when performing goal-directed tasks, but the neuronal changes that could mediate this reward-directed learning are not well understood. Tye et al. trained rats to self-administer a sucrose reward, and show that reward learning depends on increased activity and synaptic strength in the amygdala, a brain region important for emotional learning. The level of learning attained by individual animals correlated well with the degree of synaptic strength enhancement. An enhanced understanding of brain changes during reward learning will aid the development of therapeutic interventions for deficits in natural reward learning or cases of aberrant reward learning, such as drug addiction, or eating disorders. Some people earn rewards more successfully when performing goal-directed tasks, but the neuronal changes that could mediate this reward-directed learning are not well understood. Rats were trained to self-administer a sucrose reward, and it was shown that reward learning depends on increased activity and synaptic strength in the amygdala, a brain region important for emotional learning. The level of learning attained by individual animals correlated well with the degree of synaptic strength enhancement. What neural changes underlie individual differences in goal-directed learning? The lateral amygdala (LA) is important for assigning emotional and motivational significance to discrete environmental cues1,2,3,4, including those that signal rewarding events5,6,7,8. Recognizing that a cue predicts a reward enhances an animal’s ability to acquire that reward; however, the cellular and synaptic mechanisms that underlie cue–reward learning are unclear. Here we show that marked changes in both cue-induced neuronal firing and input-specific synaptic strength occur with the successful acquisition of a cue–reward association within a single training session. We performed both in vivo and ex vivo electrophysiological recordings in the LA of rats trained to self-administer sucrose. We observed that reward-learning success increased in proportion to the number of amygdala neurons that responded phasically to a reward-predictive cue. Furthermore, cue–reward learning induced an AMPA (α-amino-3-hydroxy-5-methyl-isoxazole propionic acid)-receptor-mediated increase in the strength of thalamic, but not cortical, synapses in the LA that was apparent immediately after the first training session. The level of learning attained by individual subjects was highly correlated with the degree of synaptic strength enhancement. Importantly, intra-LA NMDA (N-methyl-d-aspartate)-receptor blockade impaired reward-learning performance and attenuated the associated increase in synaptic strength. These findings provide evidence of a connection between LA synaptic plasticity and cue–reward learning, potentially representing a key mechanism underlying goal-directed behaviour.