Friday, April 4, 2025
4/4/2025
Neuronal and theoretical analysis of subjective value representations - PROJECT SUMMARY Dysfunctional decision making has devastating impacts on individuals and on society. Many types of decision making are therefore under vigorous investigation. This proposal emphasizes value-based decisions, in which choosers select among options based on their subjective assessment of value. A deeper understand- ing of this behavior is needed to develop the best possible treatments for decision making disorders, including many forms of addiction and cognitive deficits that accompany mental illness, brain injury, and neurodegenera- tive disease. Consumer choice is one of the best studied forms of value-based decisions. Studies reveal that our economic personalities have a significant genetic basis, but it is difficult to trace causal links between genes and behavior in humans. In response, geneticists often turn to simpler invertebrate organisms like the nema- tode worm C. elegans in which the functions of genes nearly identical to their human equivalents can be inves- tigated more rapidly, completely, and at a fraction of the cost. Until now, evidence that nematodes are truly ca- pable of value-based decision making has merely been suggestive. However, economists have developed mathematically rigorous testing procedures for determining whether decisions are based on subjective value. The PI's laboratory has developed microfluidic devices that enable this test to be done on nematodes deciding between high-quality food that is relatively abundant and low-quality food that is more scarce. The results meet all the criteria of value-based decision making. Previous work in the PI’s laboratory and others has delineated the neural circuits for all three of the main foraging behaviors of C. elegans. At the same time, whole-brain neuronal imaging has come of age in this organism, including transgenic strains in which essentially all neurons in the brain can be identified unam- biguously. Capitalizing on these new developments, the proposed research address three broad yet interre- lated questions: How is subjective value represented? How is subjective value translated into action? How is subjective value learned? How is subjective value altered by drugs of abuse? Successful completion of the proposed research yields a biologically realistic computational model of the neuronal mechanism of value-based decision making in a compact circuit than can, in principle, be under- stood completely. This work provides a foundation for understanding value-based decisions in more complex organisms. The work also lays the cornerstone for genetic analyses, at single-neuron resolution, of orthologs of human genes identified in association studies related to decision making. The research is broadly significant because it establishes a new biological system in which to analyze at single-neuron resolution the interaction of genes previously associated with decision making in humans, and to discover novel genetic pathways in- volved in this behavior.
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