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|Title:||Behavioral and dopaminergic representations of social stress, resilience, and reward|
|Advisors:||FalknerWitten, AnnegretIlana LB|
|Publisher:||Princeton, NJ : Princeton University|
|Abstract:||This thesis investigates behavioral and dopaminergic responses to social stress and reward in mice, and how these responses change with experience. Dopamine is a neuromodulator essential for reward-based learning, its release being causal in associating neutral sensory cues or actions with a paired reward. The types of rewards dopamine is known to respond to are diverse: including food, social interactions, and relief. These reward modalities have typically been studied in seperate, highly controlled task contexts. In the two studies presented here, I add to the growing set of literature examining the role of dopamine in more complex naturalistic settings and the diversity in response profiles across individual dopamine neurons. In the first study, I investigate the role of dopamine in driving individual differences in response to chronic stress. I record dopaminergic neural activity and behavior during chronic social defeat (in which a mouse contends with attacks from novel aggressors for ten days) and utilize machine learning methods for behavior quantification to show that stress-susceptible animals have elevated relief signals, while animals resilient to stress have dopaminergic reinforcement of self-defense behavior. Optogenetic activation of dopaminergic neurons during defeat stress was sufficient to promote resilience and to increase self-defense when stimulation was specifically directed to this behavior. Thus, I show how dopamine can causally influence complex social behaviors in a mouse model of stress. In the second study, using 2-photon calcium imaging of single dopamine neurons, I explore if the same or different neurons respond to two different types of rewarding stimuli: food and social targets (novel mice). Social responses were found in a small population of neurons that significantly overlapped with the food-responsive population. The size of the population with overlapping responses grew when animals had increased motivation for food (when hungry) or for social interaction (after virgin mice were given opposite-sex exposure). The significant overlap between neurons responding to food and social stimuli suggests that there are not functionally distinct subpopulations responsible for driving food- and social-driven motivation. Together these studies increase our understanding of how dopaminergic neurons encode social information in stressful and rewarding contexts.|
|Type of Material:||Academic dissertations (Ph.D.)|
|Appears in Collections:||Neuroscience|
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