Neural Circuits mediating Innate Behaviors

Animals in the wild encounter many types of external stimuli such as threat and food, and must exhibit appropriate responses for survival. How does a brain recognize such stimuli with sensory systems, create internal representations of these external stimuli, and then elicit appropriate behavioral responses? Single-gene approaches have been instrumental in elucidating signaling pathways mediating innate behaviors. However, it is important to recognize that the building blocks of the nervous system are individual neural circuits whereas genes are the functional units of the signaling pathways. Consistent with these, similar behaviors can be mediated by the same signaling pathway, but are processed in distinct neural circuits. For example, fear memory and spatial memory are both controlled by cAMP signaling and similar cellular mechanisms of neuronal plasticity, but they are processed in different circuits; fear memory by the amygdala and spatial memory by the hippocampus.
    To address this problem, our laboratory applies combinatory approaches and uses the fruit fly, Drosophila melanogaster, because of a wealth of genetic tools available, a relatively simple brain, and a complex, interesting behavioral repertoire. Rapidly emerging tools also permit relatively facile identification of neural circuits. Drosophila has been used, through single-gene approaches, to dissect fundamental behaviors such as circadian rhythm, learning & memory and courtship behavior. To this end, many behavioral genes and their signaling pathways are conserved from flies to humans. Likewise we anticipate the principles learned from circuit analyses in flies will be applicable to mammals. Our current objective is to identify neurons that subserve a particular innate behavior, learn the organization of their neuronal projections, apply imaging and electrophysiology techniques to probe their activity, and therefore define precisely contributions of each set of neurons to the behavior
    I developed a novel behavioral paradigm in Drosophila based on an observation that Seymour Benzer made over 35 years ago. This paradigm involves avoidance of a substance, called Drosophila Stress Odorant (or dSO), which is emitted by flies subjected to mechanical stress or electrical shock. Most naive flies choose the fresh tube when given a choice, in a T-maze, between a fresh tube and a conditioned tube in which emitter flies were previously stressed. Through Gas Chromatography & Mass Spectometry analysis, I identified CO2 as one component of dSO. In collaboration with Richard Axels laboratory, we next identified olfactory sensory neurons activated by CO2 through calcium imaging. These neurons express the Gr21a receptor and innervate the V glomerulus in the antennal lobe (AL). They are both necessary and sufficient for avoidance to CO2. These experiments together indicate that Gr21a+ expressing neurons are dedicated to detecting CO2, and that avoidance to CO2 is likely mediated by a dedicated circuit. It is worth emphasizing that the CO2 neuron is a rare example of object detector found in the peripheral nervous system. Several lines of evidence indicated that an additional component(s) besides CO2 exists in dSO. Consistent with this idea, I recently discovered candidate compounds to potentate the effects of CO2 during avoidance response. We are following up the studies.
    These studies described above demonstrate that we can map neural circuit to a particular behavior using molecular genetic approaches combined with calcium imaging and electrophysiological techniques. In my laboratory, I would like to use similar approaches to address a slightly different problem. Stimuli such as CO2 elicit the same stereotypic response- avoidance- whether flies were starved or were altered in their circadian rhythm. Conversely, other stimuli generate behavioral responses largely influenced by the internal state of animal. I have observed that avoidance or attraction (or valence) to appetitive odor in a simple T-maze is dependent on the satiety or hunger state of flies. Starved flies are attracted to appetitive odor whereas satiated flies are repelled by the same odor. This switch (or satiety induced valence switch) is specific to appetitive odor as many chemical odors tested thus far did not render flies to undergo the switch- both starved and satiated flies exhibited the same response to each chemical odor, whether it is attractive or aversive. This result suggests that although appetitive odor is a complex mixture of compounds, it presents as unitary percepts to the fly. These observations suggest the hypothesis that the fly has a group of neurons or grandmother cells essential for recognition of the important stimulus and their activity is modulated by the satiety state.