UC Berkeley

Stress and motivation are inextricably intertwined. Importantly, stress, especially early in life, is associated with increased substance use and risk of addiction. Furthermore, there is high co-morbidity between stress-induced disorders such as PTSD and motivation disorders such as addiction and depression. This is suggestive of an overlapping neurobiological mechanism of vulnerability. The prefrontal cortex (PFC) is implicated in both stress and motivation circuitry and thus, may be a critical link between the two. It is highly connected to limbic regions, including the amygdala and hippocampus, as well as to regions crucial for motivation and reward such as the striatum and ventral tegmental area (VTA). The PFC is also highly sensitive to stress and has an extended period of experience-dependent plasticity as it continues to develop through adolescence. Thus, it is important to understand PFC circuitry, how it changes over development in response to stressors and how factors such as stressor type and sex might contribute to individual variability following stress exposure.

In this thesis, I explore the role of prefrontal cortex circuitry in both stress and motivated behaviors using rodent models. In chapter one, I introduce the stress response, the relationship between stress and motivated behaviors, and describe the prefrontal cortex systems that connect them. In chapter two, I elaborate on part of this circuitry, describing the anatomy of VTA dopaminergic and GABAergic projections to PFC subregions, as well as to other limbic brain areas. In chapter three, I investigate how responding to the distress of another (vicarious stress) leads to biased motivated helping behavior depending on group membership and I describe the neural circuits underlying this behavior. Further, I address how helping behavior and the neural circuits involved change across development. I present evidence that in-group biases arise over development and that pro-social intent toward ingroup members recruits distinct neural circuits. In chapter four, I explore the effects of an acute traumatic stressor on PFC oligodendrocytes and myelination. I show there are sex-specific differences; females are preferentially affected, displaying stress induced increases in PFC myelin in the short term, yet decreased myelination in the long term relative to controls. Finally, I provide closing thoughts, offer future directions, and elaborate on the relevance of the PFC in human disorders. Overall, this body of work provides insight into stress and motivation circuitry, with a focus on the prefrontal cortex.