Basolateral amygdala regulation of cellular and chemical signals within the nucleus accumbens during conditioned reward-seeking.

摘要

Rewards are not procured and consumed in a vacuum. Rather, successful pursuit of reward occurs in a diverse, dynamic environment. As such, the ability to form and maintain associations between environmental cues, actions, and rewarding stimuli is a fundamental aspect of goal-directed behaviors. The adaptive significance of these associative processes is abundantly clear, as organisms that can better predict, procure and consume rewards using environmental cues will enjoy increased success in future decision-making. Numerous lines of research have identified that associative reward processing is mediated by a distributed network of brain nuclei that includes the nucleus accumbens (NAc) and its innervation from dopamine neurons located in the midbrain. However, the precise neural processing, and neural circuitry that mediates these associative processes remain unclear. This dissertation seeks to dissect the contribution of one corticolimbic input, the basolateral amygdala (BLA), to neurochemical and neurophysiological signaling within the NAc. The first set of experiments detailed in this dissertation took advantage of technological advances to characterize patterns of NAc dopamine release in real time, during cued-instrumental responding for a natural reinforcer, and determine the contribution of the BLA to these signals. The results of the first experiment demonstrate for the first time that rapid dopamine release in the NAc and conditioned responding to reward-predictive stimuli are functionally mediated by the BLA. The second set of experiments examined the contribution of the BLA to the post-synaptic signaling of NAc neurons, demonstrating that the BLA facilitates excitatory encoding of reward-predictive cues within the NAc, during cued-instrumental responding for a natural reward. The final experiments described in this dissertation examined how these associative reward signals within the NAc and demonstrate that the BLA contributes to conditioned neural excitations within the NAc during cocaine self-administration, while also regulating the tonic firing rate of phasic inhibitions. Together, these experiments provide novel characterizations of the neural circuits and mechanisms by which environmental stimuli are processed within the brain, providing insight into the potential role of the BLA-NAc circuit in mediating psychiatric disorders, such as drug addiction, which are characterized by maladaptive goal-directed behavior and associative reward processes.