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.
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.
|Gonzalez-Suarez, Aneysis D; Nitabach, Michael N (2018) Peptide-Mediated Neurotransmission Takes Center Stage. Trends Neurosci 41:325-327|
|Hughes, Michael E; Abruzzi, Katherine C; Allada, Ravi et al. (2017) Guidelines for Genome-Scale Analysis of Biological Rhythms. J Biol Rhythms 32:380-393|
|Chen, Dandan; Sitaraman, Divya; Chen, Nan et al. (2017) Genetic and neuronal mechanisms governing the sex-specific interaction between sleep and sexual behaviors in Drosophila. Nat Commun 8:154|
|Ghosh, D Dipon; Nitabach, Michael N; Zhang, Yun et al. (2017) Multisensory integration in C. elegans. Curr Opin Neurobiol 43:110-118|
|Ghosh, D Dipon; Sanders, Tom; Hong, Soonwook et al. (2016) Neural Architecture of Hunger-Dependent Multisensory Decision Making in C. elegans. Neuron 92:1049-1062|
|Raccuglia, Davide; McCurdy, Li Yan; Demir, Mahmut et al. (2016) Presynaptic GABA Receptors Mediate Temporal Contrast Enhancement in Drosophila Olfactory Sensory Neurons and Modulate Odor-Driven Behavioral Kinetics. eNeuro 3:|
|Sitaraman, Divya; Aso, Yoshinori; Rubin, Gerald M et al. (2015) Control of Sleep by Dopaminergic Inputs to the Drosophila Mushroom Body. Front Neural Circuits 9:73|
|Sitaraman, Divya; Aso, Yoshinori; Jin, Xin et al. (2015) Propagation of Homeostatic Sleep Signals by Segregated Synaptic Microcircuits of the Drosophila Mushroom Body. Curr Biol 25:2915-27|
|Kunst, Michael; Tso, Matthew C F; Ghosh, D Dipon et al. (2015) Rhythmic control of activity and sleep by class B1 GPCRs. Crit Rev Biochem Mol Biol 50:18-30|
|Gui, Junhong; Liu, Boyi; Cao, Guan et al. (2014) A tarantula-venom peptide antagonizes the TRPA1 nociceptor ion channel by binding to the S1-S4 gating domain. Curr Biol 24:473-83|
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