Jing W. Wang
e-mail: jw800@ucsd.edu |
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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.
Suh, G.S.B., Wong, A.M., Hergarden,
A.C., Wang, J.W., Simon, A., Benzer, S., Axel, R., and Anderson,
D.J. (2004). A single population of olfactory sensory neurons
mediates an innate avoidance behavior in Drosophila. Nature.
431:854-9.
Wang, J.W., Wong, A.M., Flores, J., Vosshall, L.B., and Axel,
R. (2003). Two-photon calcium imaging reveals an odor-evoked
map of activity in the fly brain. Cell 112:271-282.
Wong, A.M.*, Wang, J.W.*, and Axel, R. (2002). Spatial representation
of the glomerular map in the Drosophila protocerebrum. Cell 109:
229-241. *These authors contributed equally to this work.
Wang, J.W., Denk, W., Flores, J., and Gelperin, A. (2001). Initiation
and propagation of calcium-dependent action potentials in a coupled
network of olfactory interneurons. J. Neurophysiol. 85: 977-985.
Wang, J.W., Humphreys, J.M., Phillips, J.P., Hilliker, A.J.,
and Wu, C.-F. (2000). A novel leg-shaking Drosophila mutant defective
in a voltage-gated K+ current and hypersensitive to reactive
oxygen species. J. Neurosci. 20: 5958-5964.
Dr. Wang received his Ph.D. in neurobiology from the University of Iowa. He did postdoctoral research in the laboratory of Alan Gelperin at Bell Labs, then in the laboratory of Richard Axel at Columbia University. Since joining the faculty in 2004, he has been named a Chris and Warren Hellman Faculty Scholar, a Searle Scholar, and a Beckman Young Investigator.
