EXCEED THE SPACE PROVIDED. Novel experimental technologies were developed to monitor and manipulate, through light, genetically circumscribed populations of neurons in vivo. These technologies will be harnessed to study information processing in the olfactory system of the fruit fly, Drosophila melanogaster. Cell-type specific promoters will target genetically encoded optical sensors and effectors to neurons in four synaptically coupled processing layers: 1) To olfactory receptor neurons, which are located at the sensory surface and project to the antennal lobe, the analog of the vertebrate olfactory bulb; 2) to local inhibitory interneurons of the antennal lobe; 3) to projection neurons that relay olfactory information from the antennal lobe to the mushroom body, the analog of the vertebrate olfactory cortex; and 4) to Kenyon cells, the intrinsic neurons of the mushroom body. Odor-evoked neural activity patterns will be visualized by optical microscopy at each of these genetically highlighted processing stages. With this innovative strategy at their core, three specific aims directed at the fundamental operational principles of a multilayered neural network will be addressed: 1) The coding formats at each of the four olfactory processing stages will be characterized by comparing the neural representations of different odors. 2) The mapping rules that relate these codes will be elucidated by tracing odor representations across stages. 3) The computational origin, physical form, and semantic content of neural symbols that express abstractions, classifications, and behavioral connotations will be studied in experiments that combine optical imaging with behavioral assays. The focus of these experiments will be on the neuronal substrate for attaching hedonic valence to odors, and on its modification by experience. The combination of a parallel optical read-out and an eminently tractable experimental system opens an opportunity to understand collective network properties in cellular or even molecular terms, and to transcend thereby some of the boundaries that currently divide neuroscience into molecular, cellular, and systems branches. Such a unified understanding will inform pathogenetic mechanisms in neurological or psychiatric disorders and disclose potential molecular targets for interventions aimed at altering network function. PERFORMANCE SITE ========================================Section End===========================================
| Sjulson, Lucas; Miesenbock, Gero (2008) Rational optimization and imaging in vivo of a genetically encoded optical voltage reporter. J Neurosci 28:5582-93 |
| Shang, Yuhua; Claridge-Chang, Adam; Sjulson, Lucas et al. (2007) Excitatory local circuits and their implications for olfactory processing in the fly antennal lobe. Cell 128:601-12 |
