To navigate complex natural environments containing both dangerous and valuable items, animals must make economic decisions on the basis of information transduced by multiple senses. Such decisions underlie key health-related behaviors, such as eating and locomotion. Even pathological behaviors, like drug addiction, are based on economic decisions, albeit maladaptive ones. It is thus essential for both basic and translational purposes to better understand the neural substrates that underlie the balancing of threat and reward. However, mammalian nervous systems are extremely complex, and this has hindered progress in uncovering fundamental neural principles of decision making. In contrast, the experimentally accessible nervous system of the nematode worm C. elegans contains only a few hundred identified neurons of defined synaptic connectivity and implements a variety of robust adaptive sensory-guided behaviors. Here we propose to use genetic, physiological, and behavioral approaches in C. elegans to pursue the long-term goal of elucidating the cellular and molecular mechanisms underlying economic decision making. Our preliminary studies lead to a model in which a higher-order sensorimotor interneuron controls the balance of threat and reward in a multisensory decision task by top-down aminergic signaling to the primary sensory neuron that detects danger to tune its sensitivity, and this aminergic signal is itself modulated by an autocrine neuropeptidergic signal acting on the higher-order interneuron. The proposed studies deploy a combination of neurogenetic, behavioral, and physiological approaches to test the detailed predictions of this model and to elucidate how internal physiological state influences economic decision making by regulating the top-down peptide-amine relay circuit.

Public Health Relevance

To navigate complex natural environments containing both dangerous and valuable items, animals must make economic decisions on the basis of information transduced by multiple senses. Such decisions underlie key health-related behaviors, such as eating and locomotion. It is thus essential for both basic and translational purposes to better understand the neural substrates that underlie the balancing of threat and reward, including their modulation by neuropeptide signaling pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM098931-05
Application #
9196718
Study Section
Special Emphasis Panel (ZRG1-MDCN-G (91)S)
Program Officer
Sesma, Michael A
Project Start
2011-09-15
Project End
2020-06-30
Budget Start
2016-09-23
Budget End
2017-06-30
Support Year
5
Fiscal Year
2016
Total Cost
$394,703
Indirect Cost
$158,603
Name
Yale University
Department
Physiology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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