Understanding how smell is transformed to behavior remains highly challenging. The higher-order olfactory centers, which are two synapses away from the periphery in insects and mammals, are crucial for interpreting the motivational significance of environmental odor cues. At present, molecular and circuit mechanisms underlying the functioning of higher-order olfactory centers have been rarely explored in any organisms. Genetically tractable Drosophila larvae have a highly evolved nervous system that is yet numerically simple. In this application, we will use the fly larva model to elucidate: 1) how a small subset of dopaminergic neurons postsynaptic to second-order projection neurons (analogous to mitral cells in mammals) receives and processes odor representations;2) how such DA neurons mediate the transformation of olfactory inputs into motivational values to drive appetite for palatable food. Our recent findings demonstrate that Drosophila larvae fed ad libitum display olfactory reward-driven appetite for palatable food, and this non-homeostatic control mechanism requires the neuropil (named the lateral horn) for higher-order olfactory processing. We have found that a small subset of DA neurons as well as four neuropeptide Y-like NPF-producing neurons project to larval lateral horns, and they mediate the transformation of odor representations to appetitive motivation. This application has three objectives: 1) Functional analyses of dopamine (DA) in reception of appetitive olfactory information;2) Genetic analysis of a neuropeptide F and other molecular pathways in DA neurons;3) Functional analyses of DA receptor neurons in transforming odor inputs to appetitive motivation. We expect that the successful outcomes from the proposed studies will provide validations of the fly larva model for elucidating the molecular and neural basis of transformation of odor representations to appetitive motivation. Such knowledge should also provide better understanding of the pathophysiology of appetite-related disorders, and aid the genetic risk assessment for such disorders.
The question of how a pleasurable food odor can potently trigger appetitive drive has been a major challenge to neurobiologists. In this proposal, we will try to validate the use of the fly model for the general understanding of how the perception of rewarding food odors and assignment of motivational significance of such odor cues by the brain is regulated by a neural circuit involving NPY family peptides and dopamine. We expect that these proposed studies may provide better understanding of the neurobiological basis of odor-induced behaviors as well as the neuropathology of olfaction dysfunction and disorders.