Gilad Barnea, Ph.D.
Robert and Nancy Carney Assistant Professor of Neuroscience
Our laboratory studies how the mammalian brain processes olfactory information and translates it into behavioral outputs. We are developing a new method for transsynaptic labeling of neural circuits combining molecular biology and mouse genetics. This method will enable us to map and characterize the neural circuits that the brain uses to process olfactory information. We also study the role of odorant receptors in the wiring of olfactory circuits. Finally, we are developing a molecular method to selectively record the activation of particular dopamine receptor subtypes in mice.
Research DescriptionThe identity of an odor is deconstructed by the nose and represented by a unique, spatially invariant, combination of structures called glomeruli in the olfactory bulb, the first relay station for olfactory information in the brain. An olfactory map of activity is thus generated in the olfactory bulb. How does the brain reconstruct the identity of an odor from a pattern of active glomeruli in the bulb? Our approach to answer this question combines molecular biology and mouse genetics to map and characterize the neuronal circuits used by the brain for processing olfactory information.
Using our knowledge of the biochemistry of signal transduction pathways, we have designed a system for trans-synaptic labeling of neurons in the mouse. The core of the system is a synthetic signaling pathway that is genetically introduced into all neurons in the animal. This signaling pathway translates the activation of an engineered receptor fusion protein into expression of a reporter gene that can be visualized. Specificity is achieved by genetically modifying the olfactory sensory neurons that express a given odorant receptor to secrete the ligand for the engineered receptor into their synapses. Binding of the ligand to its receptors on the projection neurons that form synapses with the modified olfactory neurons will activate the signaling pathway, leading to expression of the reporter gene only in these cells. In this manner, only this subset of projection neurons will be visualized. Our experimental design is not limited to tracing experiments. Since the system is modular, it can be readily adapted for functional studies, in which we will genetically modify a given neuronal circuit and study the behavioral consequences. Ultimately, these studies may elucidate the mechanisms used by the brain to identify odors and to translate this information into behavioral outputs.
Grants and Awards2008 Pew Scholar in the Biomedical Sciences
2009 Kavli Fellow, National Academy of Science
2012 - Robert and Nancy Carney Assistant Professor of Neuroscience
AffiliationsSociety for Neuroscience
Funded ResearchCurrent grants:
Pew Scholar in the Biomedical Sciences
The Pew Charitable Trusts
"Mapping the neural projections from the olfactory bulb of the mouse by a new technique for trans-synaptic labeling"
$240,000 over four years
Role: Principle investigator
NIH 5 R01 MH086920-02
National Institute of Mental Health, National Institutes of Health-EUREKA
"A Molecular Method to Selectively Record Activation of Dopamine Receptor Subtypes"
$800,000 direct costs over four years
Role: Principle investigator
Supplement to above EUREKA grant
$150,000 direct costs over three years
Role: Principle investigator
CVR pilot grant
Center for Vision Research, Brown University
"Identifying ligands for the receptor GPR161 that is implicated in congenital cataracts"
$5,000 (additional $5,000 for Carthene Bazemore-Walker)
Role: Principal investigator
My main teaching commitment is as director of one of the core courses of the Neuroscience Graduate Program (NEUR 2040). In this course, we discuss topics in molecular and developmental neurobiology, with a special emphasis on the use of molecular genetics to study the nervous system. I also direct a seminar course for undergraduate students (NEUR 1940). The focus of this course is on the interplay between genes, neural circuits and behavior. In addition, I periodically present guest lectures in other courses.
- Advanced Molecular and Cellular Neurobiology II (NEUR 2040)
- Molecular Neurobiology: Genes, Circuits and Behavior (NEUR 1940)
- Inagaki, H. K., Ben-Tabou de-Leon, S., Wong, A. M., Jagadish, S., Ishimoto, H., Barnea, G., Kitamoto, T., Axel, R. and Anderson, D. J. (2012) Visualizing Neuromodulation In Vivo: TANGO-Mapping of Dopamine Signaling Reveals Appetite Control of Sugar Sensing. Cell. 148, 583-595. PMCID: PMC3295637 (2012)
- Cao, L., Benz, E. G., Schrank, B. R., Rickenbacher, G. T., Gomez, A. C., Rodriguez, S., Levites, Y., Edwards, S. R., Golde, T., Hyman, B. T., Barnea G. and Albers, M. W. Aβ alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo. (Nature Communications In Press). (2012)
- Johnson, M. A, Tsai, L., Roy, D, Valenzuela, D. H., Mosley, C., Magklara, A., Lomvardas, L., Liberles, S. D. and Barnea, G. (2012) Neurons expressing trace amine-associated receptors project to discrete glomeruli and constitute an olfactory subsystem. Proc. Natl. Acad. Sci. USA. Published ahead of print July 26, 2012, doi:10.1073/pnas.1206724109. (2012)
- Magklara, A., Yen, A., Coquitt, B. M., Clowney, E. J., Allen, W., Markenscoff-Papadimitriou, E., Evans, Z., Kheradpour, P., Mountoufaris, G., Carey, C., Barnea, G., Kellis, M. and Lomvardas, S. (2011) An Epigenetic Signature for Monoallelic Olfactory Receptor Expression. Cell. 145, 555-570. PMCID: PMC3094500 (2011)
- Barnea, G., Strapps W., Herrada G., Berman Y., Ong J., Kloss B, Axel R., and Lee K. J. (2008) The genetic design of signaling cascades to record receptor activation. Proc. Natl. Acad. Sci. USA. 105, 64-69. (2008)
- Lomvardas, S., Barnea, G., Pisapia, D., Mendelsohn, M., Kirkland, J., and Axel, R. (2006) Interchromosomal interactions and olfactory receptor choice. Cell. 126, 403-413. (2006)
- Shykind, B.M., Rohani, S.C., O'Donnell, S., Nemes, A., Mendelsohn, M., Sun, Y., Axel, R., and Barnea, G. (2004). Gene switching and the stability of odorant receptor gene choice. Cell. 117, 801-815. (2004)
- Yu, C.R., Power, J., Barnea, G., O'Donnell, S., Brown, H.E.V., Osborne, J., Axel, R., and Gogos, G.A. (2004). Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map. Neuron. 42, 553-566. (2004)
- Barnea, G., O'Donnell, S., Mancia, F., Sun, X., Nemes, A., Mendelsohn, M., and Axel, R. (2004). Odorant receptors on axon termini in the brain. Science. 304, 1468. (2004)