Division of Biological Sciences
University of California, San Diego
2218 Bonner Hall, MC 0368
La Jolla, CA 92093-0368
2005 Searle Scholar
Neural Bases of Olfactory Behariors
Most animals are endowed with an olfactory system that is essential for finding foods, avoiding predators, and locating mating partners. Several key findings made in the last decade or so have shaped our understanding of the olfactory sense, particularly the discovery of a large family of some 1,000 different olfactory receptor genes in the mouse genome. Each receptor neuron expresses just one receptor gene and neurons expressing the same receptor gene converge with high accuracy onto a single glomerulus in the olfactory bulb, establishing the notion that the olfactory system employs spatial segregation of sensory input to encode the quality of odors.
An array of powerful genetic tools is available in Drosophila to label and manipulate a subpopulation of neurons within a circuit, making it an attractive model system to study the mechanism of olfaction. How is olfactory information represented and processed in the fly central nervous system? This question is the main driving force for research in my laboratory.
A functional map of odor-evoked activity in the antennal lobe visualized by two-photon calcium imaging
My collaborators and I have developed an imaging system that couples two-photon microscopy with the specific expression of the calcium-sensitive fluorescent protein, G-CaMP. We discovered that a given odorant elicits a distinct spatial pattern of activity in the antennal lobe, demonstrating a functional map of olfactory activity in the antennal lobe. By comparing odor responses of sensory neuron axons and dendrites of projection neurons (PNs) in the same glomerulus with the expression of G-CaMP in only one cell type, we found similar odor-evoked activity in both pre- and postsynaptic cells, which suggests that activity in PNs derives mainly from their cognate sensory neurons. We have begun to map olfactory activity in the fly brain with this imaging technique. By expressing G-CaMP in all neurons, we identified the V glomerulus as the only region in the antennal lobe that shows response to CO2, which elicits innate avoidance behavior in the T-maze paradigm. Inhibition of neural transmission in receptor neurons that converge onto the V glomerulus, using a temperature-sensitive mutant Shibire gene (Shts1), blocks the avoidance response to CO2, suggesting that the functional map is required for behavioral output.
A spatial map of glomerular connection in higher brain centers
By emplying the FLP-out technique to generate flies containing only one labeled PN, we are able to relate the axonal arbor with the glomerulus a given PN innervates. We discovered that the patterns of axonal arborization of PNs from the same glomerulus are conserved between different animals. PNs innervating the same glomerulus exhibit remarkably similar axonal patterns in the protocerebrum and PNs coming from different glomeruli display different axonal topography. Therefore, a spatial map of olfactory information is retained in higher brain centers. Axonal arbors of different PNs exhibit overlapping distribution in the protocerebrum, suggesting that third order neurons residing in the protocerebrum may integrate olfactory information from multiple glomeruli.
By integrating several neural techniques, including single-neuron electrophysiology, optical imaging with genetically encoded activity indicators and genetic tools to silence or activate specific neurons in the stereotypic olfactory circuit, we hope to understand the neuronal bases of olfactory behaviors and test different hypotheses of olfactory codes with unprecedented resolution.