Reverse Engineering the Fruit Fly Brain
Our research focuses on Drosophila as an attractive model system for understanding the logic of olfactory perception because a fruit fly (i) exhibits complex olfactory-driven behaviors, (ii) has a nervous system that is numerically five orders of magnitude smaller than that of vertebrates (the fly brain contains approximately 100,000 neurons) and, (iii) makes it possible to use an extensive genetic toolbox to visualize and alter neural circuits in the olfactory system. One additional factor that makes Drosophila so attractive for olfactory research is (iv) the uniquely comprehensive description of its sensory periphery, including a complete molecular characterization of olfactory sensory neurons and their projections into the brain. All of these factors make Drosophila a powerful system for analyzing the neural circuit basis of behavior and provide an unmatched platform for investigating the logic of olfactory information processing in the brain.
Biological Validation of Neural Circuit Models of the Fruit Fly Brain
Efforts at reverse engineering the brain must ultimately confront the need to validate hypotheses regarding neural information processing against actual biological systems. In order to achieve biological validation of the Neurokernel, the computational modeling of the fly brain must be tightly integrated with increasingly precise electrophysiological techniques and the recorded data evaluated with novel system identification methods. This will enable direct comparison of the output of models executed by Neurokernel to that of corresponding neurons in the brain regions of interest.
The methodology for the biological validation of Neurokernel circuits and architectures is schematically depicted below.
Neural responses to sensory stimuli are recorded from the live fly brain in real time and compared to the computed responses of the corresponding components in a fly brain model executed on the same time scale. Discrepancies between these responses and new connectome data may be used to improve the model's accuracy
Reverse Engineering the Early Olfactory System of the Drosophila
We believe that the lack of a deeper understanding of how Olfactory Sensory Neurons (OSNs) encode odors has fundamentally hindered progress in understanding olfactory signal processing in higher brain centers. Moreover, the lack of precise stimulus delivery and measurement systems has fundamentally limited the progress of system identification in olfaction.
To address this limitation, we developed a novel in vivo experimental setup with precise and reproducible delivery of airborne stimuli. This experimental setup enabled us to apply system identification methods to OSNs in Drosophila. Currently, we are applying time-varying odor stimuli and are recording in vivo the response of Projection Neurons (PNs) postsynaptic to OSNs. These novel recordings have shown that individual OSNs and PNs encode the gradient and acceleration of odor concentration waveforms, respectively. This research was performed in collaboration with Dr. Richard Axel in the Axel Laboratory.
- Anmo J. Kim, Aurel A. Lazar and Yevgeniy B. Slutskiy, System Identification of Drosophila Olfactory Sensory Neurons , Journal of Computational Neuroscience, Vol. 30, No.1, February 2011, pp. 143-161, Special Issue on Methods of Information Theory.
- A.J. Kim, A.A. Lazar, and Y.B. Slutskiy, Projection Neurons in Drosophila Antennal Lobes Signal the Acceleration of Odor Concentrations, eLife 2015;10.7554/eLife.06651, June 2015.
- A.A. Lazar and C.-H. Yeh, Functional Identification of an Antennal Lobe DM4 Projection Neuron of the Fruit Fly, Computational Neuroscience Meeting, Volume 15, July 2014, Québec City, Canada.