Date of Award

Summer 2017

Document Type


Degree Name

Doctor of Philosophy (PhD)


Biomedical Sciences

First Advisor

Wheeler, Robert

Second Advisor

Blackmore, Murry

Third Advisor

Gasser, Paul


Humans and animals are constantly exposed to external stimuli. The ability to process reward value of a stimulus is critical to guiding appropriate behavior and essential for survival. These processes are regulated by neuronal activity and neurochemical signaling in the reward circuitry, particularly in the nucleus accumbens (NAc). The NAc receives dopaminergic inputs from the midbrain ventral tegmental area (VTA) and sends GABAergic projections to the ventral pallidum (VP). Electrophysiological studies have characterized phasic neuronal responses in the NAc that differential encode appetitive and aversive taste stimuli. Exposure to an appetitive taste stimulus evoked predominantly phasic inhibitory responses in the NAc whereas a majority of responses to an aversive taste was excitation. The work presented here focused on investigating how activity in the NAc modulate reward encoding in downstream VP, and the role of dopamine signaling in regulating neuronal responses to reward in the NAc. Using electrophysiological recording techniques, we present evidence of neural encoding of reward information in the VP. VP neurons responded to appetitive and aversive taste stimuli with primarily inhibitory and excitatory responses, respectively. Furthermore, devaluation of the appetitive stimulus resulted from cocaine-induced taste aversion conditioning revealed that the encoding of sucrose shifted from inhibition to excitation, resembling that of an aversion response. These data suggest that the VP, similar to the NAc, also encode reward information neuronally. In a subsequent study, the influence of NAc on VP reward encoding was tested by pharmacologically manipulating activity in the NAc while monitoring the neuronal activity in the VP. We demonstrate that by inhibiting activity in the NAc with a GABAergic agonist, the neural encoding to sucrose in the VP was augmented, followed by increased sucrose consumption. These findings support the notion that at least some aspect of reward information processed in VP is modulated by NAc activity. In the final study, we show that chemogenetically suppressing activity of VTA dopamine neurons inverted the response profile to sucrose from inhibition to excitation in the NAc. This elimination of inhibitory reward encoding in the NAc was accompanied by a dampened motivational state, demonstrated by subjects terminating leverpress behavior for sucrose reward quicker in a progressive ratio test on day that dopamine signaling was chemogenetically suppressed but not in control condition. Taken together, results from these studies provide insights into how reward information is represented by physiological events in the reward circuitry. We demonstrate that neuronal responses in both the NAc and the VP encode reward and correlate strongly to reward-driven motivated behavior. Furthermore, we used a chemogenetic approach to show that suppressed NAc dopamine signaling models a low motivational state that is represented by altered neuronal responses in the NAc. This endeavor to better understand the neural representation of reward may help us better understand the physiology of both normal and diseased motivational and affective states.