Most behavioral responses to odors require experience and learning before an odor stimulus acquires its value for the organism. There are however some odors that elicit innate and stereotyped behavioral responses. Some of these odors are pheromones while others are environmental odors with special selective importance for the survival of the organism. It is believed that innate behaviors are governed by genetically programmed, hard-wired neural circuits. The existence of several layers within the circuit allows for modulation of the response to reflect the internal state of the organism. Due to lack of tools for specific and sensitive trans- synaptic labeling of neurons within a circuit, little is known abut the circuit level of the brain, including hard- wired circuits. We have combined molecular biology and genetics to develop a new technique for circuit mapping in fruit flies. At the core of our system is a synthetic signaling pathway that is introduced into all neurons. Selective activation of this pathway within a particular circuit will be used to trace projections within the circuit orto alter its function. To achieve this, we will genetically modify pre-synaptic neurons, for which there is a genetic marker, such that they will express in their synapses a membrane-bound ligand that will activate the signaling pathway in post-synaptic partners. Here we propose to optimize this technique for tracing projections of second and third order neurons within the olfactory circuits. Since our system is modular, its use will be readily expanded to multiple neural circuits in the fly. Furthermore, it will be also easily adapted to experiments in which the properties of particular circuits will be modified and the functional consequences will be studied. Once we optimize our trans-synaptic tracing technique, we intend to use it to trace circuits that mediate olfactory-governed innate aversion and attraction in flies. We also intend to follow this proof of concept in flies by establishing an equivalent technique for labeling circuits in mice.
We propose to develop a new technology for mapping olfactory neural circuits in flies and manipulating their function. Better understanding of insect olfactory processing may lead to new means of protection against insect-borne diseases that are a major cause of human mortality around the globe. In addition, our technology may provide insight into the molecular and anatomical underpinnings of olfactory loss in humans due to aging or neurodegenerative diseases.
| Talay, Mustafa; Richman, Ethan B; Snell, Nathaniel J et al. (2017) Transsynaptic Mapping of Second-Order Taste Neurons in Flies by trans-Tango. Neuron 96:783-795.e4 |
