The Center of Attention: the Locus Coeruleus' Role in Dopamine Dynamics

Abstract

Arousal is essential for survival, and maladaptive arousal processing leads to inability to focus, anxiety-like behavior, and dysregulated affective states which implicate the locus coeruleus. The locus coeruleus (LC) is a major source of norepinephrine (NE) in the brain that projects to distinct brain regions which modularly influence arousal, anxiety, learning, and exploration, among other behavioral states. Recent timely studies have implicated dopamine (DA) as also co-released from the LC, yet definitive measures of release across regions, stimulus paradigms, and behaviors typically associated with the LC-NE system remain controversial. In this thesis, I utilize recently developed tools to establish catecholamine dynamics and more specifically the boundaries of LC-DA release, in appetitive and aversive behaviors. In Chapter 1, I review the current understanding of LC-evoked DA release and NE and DA release downstream of LC in a variety of behaviors. Next, I characterize the limitations of modern neuromodulator detection tools (Chapter 2). In Chapter 3, I establish baseline NE and DA dynamics in response to a variety of aversive, appetitive, and neutral stimuli in basolateral amygdala (BLA) and hippocampus (CA1). In Chapter 4, I address limitations in the biosensors used in detection of catecholamines. Then, I characterize evoked dopamine from LC terminals in CA1 and BLA. Lastly, I demonstrate that the LC releases DA during aversive and appetitive stimuli. In Chapter 5, I discuss the findings of this thesis in relationship with existing literature and outline future work that would meaningfully build on my dissertation work. My dissertation work expands our understanding of the LC's role in releasing DA and provides context for how maladaptive LC activity may affect DA signaling in aversive and appetitive conditions.