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嗅觉神经元中的神经肽直接引导果蝇饥饿时的觅食行为

时间:2011-04-20 16:08来源:Jing W. Wang 作者:admin 点击:

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Jing W. Wang

Jing W. Wang

Associate Professor
Section of Neurobiology, UCSD

e-mail: jw800@ucsd.edu
Lab Homepage: Wang Lab

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 the Wang lab.

A functional map of odor-evoked activity in the antennal lobe

    We 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 first olfactory processing center. Despite many local interneurons connecting many different glomeruli, activity of the antennal lobe output projection neurons (PNs) derives mainly from their cognate sensory neurons of the same glomerulus. We have begun to map olfactory activity in the fly brain with this imaging technique. In the antennal lobe, the V glomerulus is dedicated to sense the aversive CO2 odor. Silencing receptor neurons that converge onto the V glomerulus abolishes behavioral response to CO2. We believe that the combination of live imaging techniques and genetic perturbation of neural activity will provide a causal link between neural activity and olfactory behaviors.

figure 1

A spatial map of glomerular connection in higher brain centers

    Employing the FLP-out technique to generate flies containing only one labeled PN, we discovered that PNs innervating the same glomerulus exhibit remarkably similar axonal patterns in the protocerebrum and PNs coming from different glomeruli display different axonal topography. Therefore, higher brain centers retain a spatial map of olfactory information. Axonal arbors of different PNs exhibit overlapping distribution in the protocerebrum, suggesting that third order neurons may integrate olfactory information from multiple glomeruli.

figure 2

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. We have identified an automatic gain control that facilitates pheromone-mediated mate localization. We found that olfactory sensory neurons express the type-B inhibitory GABA receptor, activation of which suppresses 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. 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.

figure 3

    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.

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