Neurophysiology and Neuropharmacology of Decisions

Abstract

Negotiating the complex decisions that we encounter daily requires coordinated neu- ronal activity. The enormous variety of decisions we make, the intrinsic complexity of the situations we encounter, and the extraordinary flexibility of our behaviors suggest the existence of intricate neural mechanisms for negotiating contexts and making choices. Further evidence for this prediction comes from the behavioral al- terations observed in illness and after injury. Both clinical and scientific evidence suggest that decision signals are carried by electrical neuronal activity and influenced by neuromodulatory chemicals. This dissertation addresses the function of two puta- tive contributors to decision-making: neuronal activity in posterior cingulate cortex and modulatory effects of serotonin. I found that posterior cingulate neurons respond phasically to salient events (informative cues; intentional saccades; and reward deliv- ery) across multiple contexts. In addition, these neurons signal heuristically guided choices across contexts in a gambling task. These observations suggest that posterior cingulate neurons contribute to the detection and integration of salient information necessary to transform event detection to expressed decisions. I also found that lowering levels of the neuromodulator serotonin increased the probability of making risky decisions in both monkeys and mice, suggesting that this neurotransmitter con- tributes to preference formation across species. These results suggest that posterior cingulate cortex and serotonin each contribute to decision formation. In addition, the unique serotonergic pro jections to posterior cingulate cortex, as well as the frequent implication of altered serotonergic and posterior cingulate function in psychiatric dis- orders, suggest that the confluence of cingulate and serotonergic activity may offer key insights into normal and pathological mechanisms of decision making.