An examination of phasic dopamine release in distinct striatal subregions during reward-directed behavior
thesisposted on 15.04.2014, 00:00 by Holden D. Brown
Learning about stimuli that signal the attainment of food and other rewards is critical for survival. Evidence suggests that the midbrain dopamine system plays a critical role in reward learning and goal-directed behavior. Recordings of midbrain dopamine neurons in awake and behaving subjects suggest that phasic dopamine signals are uniformly broadcast throughout terminal regions in response to unpredicted reward or environmental stimuli that predict reward. However, studies sampling dopamine release from the nucleus accumbens during unpredicted reward or predictive stimuli show that phasic dopamine signaling may occur in a more regionally-selective manner. However, there has not been a systematic examination of whether phasic dopamine release from dorsal and ventral striatal subregions occurs uniformly throughout the striatum or in a regional-selective manner. To address this, I measured phasic dopamine release, using fast-scan cyclic voltammetry, in four striatal regions (nucleus accumbens shell and core, dorsomedial and dorsolateral striatum) during electrical stimulation of the ventral midbrain, unpredicted food reward or during a discriminative stimulus paradigm. The results from all experiments indicate that dopamine signaling occurs in a regional-specific manner. Electrical stimulation of the SNpc/VTA evoked dopamine release in all striatal regions but the rate of reuptake was fastest in the dorsolateral striatum and slowest in the nucleus accumbens shell. Unpredicted food reward only evoked phasic dopamine release in the nucleus accumbens core. In the discriminative stimulus task, a cue predictive of reward evoked a phasic dopamine signal in the nucleus accumbens core and dorsomedial striatum. Following performance of the discriminative stimulus task, unpredicted food reward increased phasic dopamine release in both the nucleus accumbens core and the dorsomedial striatum. No condition evoked phasic dopamine release in the nucleus accumbens shell or dorsolateral striatum. These findings provide the first demonstration that phasic stimulation, reward stimuli and reward predictive cues evoke highly compartmentalized changes in phasic dopamine release across multiple striatal regions. This incongruence with electrophysiological recordings may be due to several factors including prior task experience, selection criterion for dopamine neuronal recording, or presynaptic modification of dopamine release. Together, these results suggest distinct roles of phasic dopamine release across striatal subregions.