Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)




College of Graduate Studies

First Advisor

Gary S. Aston Jones

Second Advisor

Lawrence J. Chandler

Third Advisor

Thomas C. Jhou

Fourth Advisor

Mark A. Eckert

Fifth Advisor

Stan B. Floresco


Appropriate modification of behavior in response to dynamic environmental conditions is essential for the adaptation and survival of most biological organisms. This adaptability allows for organisms to maximize the benefit of behavior related energy expenditure (utility) while minimizing cost. Modern theories of locus coeruleus (LC) function implicate a pivotal role for the noradrenergic (NA) nucleus in mediating switches between focused behavior during periods of high utility (exploit) versus disengagement of behavior and exploration of other, more rewarding opportunities. Two modes of activity in LC neurons have been well characterized. During periods of accurate and focused behavior, LC neurons exhibit suppressed baseline activity and task-related phasic bursts. However, as focus and accuracy wanes, phasic activity is suppressed and baseline (tonic) impulse activity is elevated. These experiments sought to exogenously induce a tonic pattern of activity in LC neurons and their medial prefrontal cortical (mPFC) efferents to test the tenets of adaptive gain theory. This theory posits that phasic activity facilitates focused task performance whereas tonic activity promotes disengagement from ongoing behaviors. Thus, tonic activation immediately following a rule change should be sufficient to improve performance on a set-shifting task. Indeed, DREADD mediated stimulation of LC terminals within the mPFC decreased trials to reach criterion. However, this effect appears to result from improved application of the new rule rather than an induction of a behaviorally flexible phenotype. Further, these results were not seen for manipulations administered within the LC. These findings may reflect a new understanding of the role of LC in set-shifting and flexible behavior.


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