The Role of the Locus Coeruleus in Decision-Making Under Uncertainty - Project Summary/Abstract
Decision-making under uncertainty is a fundamental behavior that is integral to animal health
and well-being, and impairments in decision-making are seen in a variety of psychiatric disorders,
including depression, anxiety, and substance abuse disorders. Accordingly, understanding the neural
mechanisms underlying decision making under uncertainty may provide insights into the mechanisms
underlying behavioral disturbances in many psychiatric disorders. Theoretical work strongly suggests
that neuromodulatory systems, particularly the locus coeruleus-norepinephrine (LC-NE) system, play
an important role in these decision processes5,6, yet predictions of this work at the neural level remain
largely untested. The proposed work will directly test predictions of one theory, the adaptive gain
theory (AGT), which predicts that the LC-NE system regulates which behavioral strategy is best
suited for the current state of the environment: exploiting available rewards or searching for better
alternatives.
To test this hypothesis, I developed a patch foraging task for rats in operant conditioning
chambers. In this task, rats must repeatedly make decisions to harvest reward from a patch, which
depletes with each harvest, or to incur a time delay to travel to a new, full patch. AGT predicts that
when large rewards are available upon entering a full patch, LC-NE neurons will exhibit phasic burst
responses that facilitate decisions to exploit the reward in a patch (harvest from the patch). As the
reward within a patch depletes, LC phasic responses will diminish and tonic or baseline firing will
increase, facilitating decisions to search for an alternative reward (travel to a new patch). To test
these predictions, in Specific Aim 1, single unit recordings of LC-NE neurons will be used to examine
whether LC-NE activity conforms to the predictions of AGT described above. In Specific Aim 2,
optogenetic manipulations will be used to examine whether LC-NE neurons exert a causal influence
on foraging decisions. The proposed research will provide the first direct test of the AGT, promising to
improve our understanding of the function of the LC-NE system and our understanding of
mechanisms underlying decision-making.
