How is olfactory information represented and processed in the central nervous system? This question is the main driving force for research in my laboratory. We choose to investigate this question in the fruit fly, because an array of powerful genetic tools is available in Drosophila to label or manipulate a subpopulation of neurons within a circuit.
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. Activity in projection neurons (PNs) derives mainly from their cognate sensory neurons. We have begun to link olfactory behaviors with activity in the fly brain. For example, G-CaMP imaging experiments show that the V glomerulus responds to the aversive odorant CO2. Silencing the V glomerulus completely abolishes the avoidance behavioral response.
A Spatial Map of Glomerular Connection in Higher Brain Centers
By employing the FLP-out technique to generate flies with only one randomly labeled PN, we are able to relate the axonal arborization pattern 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.
Automatic Olfactory Gain Control
Animals in the environment use their sense of smell to find food and mating partners. During this process, the olfactory system must detect odors across an enormous range of intensities, and therefore must be able to regulate the sensitivity of the sensory neural circuit. How the olfactory system achieves this, has been poorly understood. In a recent work, we have identified an automatic gain control that improves pheromone-mediated mate localization.
We found that the type-B inhibitory GABA receptor is expressed in olfactory sensory neurons and works to suppress synaptic input to the fly brain. The suppression of sensory input by the inhibitory receptor is scalable, such that it kicks in most when the signal is very strong, thereby providing a gain control mechanism that turns down the dial on high intensity stimuli. We found that removal of the inhibitory receptor from olfactory sensory neurons eliminates this gain control and impairs male flies¡¯ ability to locate females. Different sensory input channels have unique gain control dials, suggesting that the ability to modulate sensitivity is wired to match the ecological needs of the of the fly¡¯s innate behaviors.
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 high resolution.
Root CM, Masuyama K, Green DS, Enell LE, Nässel DR, Lee CH, Wang JW.(2008) A presynaptic gain control mechanism fine-tunes olfactory behavior. Neuron. 59:311-21.
Root CM, Semmelhack JL, Wong AM, Flores J, Wang JW.(2007) Propagation of olfactory information in Drosophila.Proc Natl Acad Sci U S A. 104:11826-31
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.