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.

The 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.

 Current Grants:

  1R01DA036894

   NIH, Director Road Map, National Institute of Drug Abuse

  “Controlling epigenetic states and nuclear architecture in the brain”

   9/15/13-5/31/18

   Role: Co-PI (Multi PI grant with Stavros Lomvardas, Columbia University)

 

    1R01DC013561

    NIH, National Institute on Deafness and Other Communication Disorders

    “An olfactory subsystem that mediates innate behaviors”

    6/09/2014-5/31/2019

    Role: Principal investigator 

 

    NIH EUREKA 1R01MH105368

    NIH, National Institute of Mental Health 

    “Functional mapping of mammalian neural circuits”

    9/15/2014-5/31/2018

    Role: Principal investigator

 

    Pew Biomedical Programs Innovation Fund

    The Pew Charitable Trusts

     “Using trans-Tango, a new circuit tracing tool in neuroscience, to track metastatic cancer”

     9/1/2017-8/31/2019

     Role: Principal investigator (Co-PI: Ben Stanger, U. Penn)

 

   Pending grants:

     1R01DC017146

     NIH, National Institute on Deafness and Other Communication Disorders

     “The neural circuits underlying gustatory perception in flies”

     7/1/2018-6/30/2023 

     Role: Principal investigator

     

    1R01DC017145

     NIH, National Institute on Deafness and Other Communication Disorders

     “Molecular and cellular analysis of accessory olfactory circuits in mice”

     7/1/2018-6/30/2023

     Role: Principal investigator

     

  Completed 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”

    7/1/2008-6/30/2012

    Role: Principal investigator

 

    NIH EUREKA 5R01MH086920

    NIH, National Institute of Mental Health 

    “A Molecular Method to Selectively Record Activation of Dopamine Receptor Subtypes”

    8/01/2009-7/31/2013

    Role: Principal investigator

 

    Supplement to the above EUREKA Grant

    NIH, National Institute of Mental Health 

    “A Molecular Method to Selectively Record Activation of Dopamine Receptor Subtypes”

    4/01/2010-3/31/2013

    Role: Principal investigator

 

    1R21DC014333

    NIH, National Institute on Deafness and Other Communication Disorders

    “Trans-synaptic tracing and manipulation of olfactory circuits in flies”

    10/01/2014-9/30/2016

    Role: Principal investigator

 

  Completed Internal Funding:

    CVR Pilot grant

    Center for Vision Research, Brown University

    “Identifying ligands for the receptor GPR161 that is implicated in congenital cataracts”

    10/1/2009-5/28/2010

    Role: Principal investigator

 

    COBRE Pilot Funds

    COBRE Center for Cancer Signaling Networks, Brown University

    “Functional characterization of the olfactory subsystem of TAAR expressing neurons”

    4/01/2012-3/31/2013

    Role: Principal investigator

 

    Brown Institute for Brain Science, Pilot Award

    “The role of gap junctions between mitral cells in olfactory coding”

    11/15/2012-11/14/2013

    Role: Principal investigator

 

    COBRE Pilot Funds

    COBRE Center for Cancer Signaling Networks, Brown University

     “The role of the odorant receptors in the formation and maintenance of the glomeruli in the olfactory bulb”

    6/01/2013-3/31/2014

    Role: Principal investigator

 

    Brown OVPR, Richard B. Salomon Faculty Research Award

    “Developing a technique for mapping and manipulating neural circuits in flies”

    2/15/2013-6/30/2014

    Role: Principal investigator

 

    Brown OVPR, Research Seed Funds

    “The role of electrical coupling between mitral cells in olfactory coding”

    4/01/2013-6/30/2014

    Role: Principal investigator

 

    Brown OVPR, Research Seed Funds

    “Establishing a technique for studying the neural circuits underlying alcohol responses in flies”

    5/01/2014-6/30/2015

    Role: Co-PI (Karla Kaun PI)

 

    Brown Institute for Brain Science, Innovation Fund

    “Establishing a new technique for circuit tracing and manipulation”

    7/01/2014-6/30/2015

    Role: Principal investigator

 

    Brown Institute for Brain Science, Innovation Fund (Renewal)

    “Establishing a new technique for circuit tracing and manipulation”

    7/01/2015-6/30/2016

    Role: Principal investigator

Sorkaç A, Moșneanu RA, Crown AM, Savaş D, Okoro AM, Memiş E, Talay M, Barnea G. "retro-Tango enables versatile retrograde circuit tracing in Drosophila." eLife, vol. 12, 2023.

Sorkaç A, Savva YA, Savaş D, Talay M, Barnea G. "Circuit analysis reveals a neural pathway for light avoidance in Drosophila larvae." Nature Communications, vol. 13, no. 1, 2022, pp. 5274.

Snell, N.J., Fisher, J.D., Hartmann, G.G. Talay, M. and Barnea, G. (2020) Distributed Representation of Taste Quality by Second-order Gustatory Neurons in Drosophila. bioRxiv 2020.11.10.377382; https://doi.org/10.1101/2020.11.10.377382

Scaplen, K.M., Talay, M., Fisher, J.D., Cohn, R., Sorkaç, A., Aso, Y., Barnea, G.* and Kaun, K.R. (2020) Transsynaptic mapping of Drosophila mushroom body output neurons. bioRxiv 2020.09.22.309021; doi: https://doi.org/10.1101/2020.09.22.309021

Fei, A., Wu, W., Tan, L., Tang, C., Xu, Z., Huo, X., Bao, H., Johnson, M., Hartmann, G., Talay, M., Yang, C., Riegler, C., Joseph, K., Engert, F., Xie, S., Barnea, G., Liberles, S., Yang, H. and Li, Q. (2020) Coordination of two enhancers drives expression of olfactory trace amine-associated receptors. bioRxiv 2020.09.10.288951; doi: https://doi.org/10.1101/2020.09.10.288951

Bashkirova, E., Monahan, K., Campbell, C.E., Osinski, J.M., Longzhi, T., Schieren, I., Barnea, G., Xie, S, Gronostajski, R.M. and Lomvardas, S. (2020) Homeotic Regulation of Olfactory Receptor Choice via NFI-dependent Heterochromatic Silencing and Genomic Compartmentalization. bioRxiv 2020.08.30.274035; doi: https://doi.org/10.1101/2020.08.30.274035

Scaplen, K.M., Talay, M., Nunez, K.M., Salamon, S., Waterman, A.G., Gang, S., Song, S.L., Barnea G. and Kaun, K.R. (2020) Circuits that encode and guide alcohol-associated preference. Elife. 2020 Jun 4;9. doi:10.7554/eLife.48730. PubMed PMID: 32497004; PubMed Central PMCID: PMC7272191.

Talay, M., Richman, E. B., Snell, N. J., Hartmann, G. G., Fisher, J. D., Sorkaç, A., Santoyo, J. F., Chou-Freed, C., Nair, N., Johnson, M., Szymanski, J.R. and Barnea, G. (2017) Transsynaptic Mapping of Second-order Taste Neurons in Flies by trans-Tango. Neuron. 96, 783–795.

Jagadish, S., Barnea, G., Clandinin, T.R. and Axel, R. (2014) Identifying functional connections of the inner photoreceptors in Drosophila using Tango-Trace. Neuron. Neuron. 83 (3): 630-644.

Tsai, L. and Barnea, G. (2014) A critical period defined by axon-targeting mechanisms in the murine olfactory bulb. Science. 344, 197-200. 

Colquitt, B., Allen, W.E., Barnea, G. and Lomvardas, S. (2013) Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons correlates with changes in gene expression and cell identity. Proc. Natl. Acad. Sci. USA. 110, 14682-14687; published online ahead of print on August 22, 2013, doi:10.1073/pnas.1302759110.

Lyons, D.B., Magklara, A., Allen, W., Goh, T., Evans, Z., Tsai, L., Barnea, G. and Lomvardas, S. (2013) An Epigenetic Trap Stabilizes Singular Olfactory Receptor Expression. Cell 154,325-336. 

Clowney, E. J., Le Gross, M. A., Mosley, C. P., Clowney, F. G., Markenskoff-Papadimitriou, E. C., Myllys, M., Barnea, G., Larabell, C. A. and Lomvardas, S. (2012) Nuclear aggregation of olfactory receptor genes governs their monogenic expression. Cell. 151, 724-737. 

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. (2012) Aβ alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo. Nat. Commun. 3:1009 doi: 10.1038/ncomms2013. 

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. 109, 13410-13415; Published ahead of print July 26, 2012, doi:10.1073/pnas.1206724109.

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.

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.

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.

Lomvardas, S., Barnea, G., Pisapia, D., Mendelsohn, M., Kirkland, J., and Axel, R. (2006) Interchromosomal interactions and olfactory receptor choice. Cell. 126, 403-413.

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.

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.

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.

Peles E, Nativ M, Campbell PL, Sakurai T, Martinez R, Lev S, Clary DO, Schilling J, Barnea G, Plowman GD, Grumet M, Schlessinger J. "The carbonic anhydrase domain of receptor tyrosine phosphatase beta is a functional ligand for the axonal cell recognition molecule contactin." Cell, vol. 82, no. 2, 1995, pp. 251-60.

Barnea G, Grumet M, Sap J, Margolis RU, Schlessinger J. "Close similarity between receptor-linked tyrosine phosphatase and rat brain proteoglycan." Cell, vol. 76, no. 2, 1994, pp. 205.

Barnea G, Grumet M, Milev P, Silvennoinen O, Levy JB, Sap J, Schlessinger J. "Receptor tyrosine phosphatase beta is expressed in the form of proteoglycan and binds to the extracellular matrix protein tenascin." Journal of Biological Chemistry, vol. 269, no. 20, 1994, pp. 14349-52.

LaForgia S, Lasota J, Latif F, Boghosian-Sell L, Kastury K, Ohta M, Druck T, Atchison L, Cannizzaro LA, Barnea G. "Detailed genetic and physical map of the 3p chromosome region surrounding the familial renal cell carcinoma chromosome translocation, t(3;8)(p14.2;q24.1)." Cancer Research, vol. 53, no. 13, 1993, pp. 3118-24

Barnea G, Silvennoinen O, Shaanan B, Honegger AM, Canoll PD, D'Eustachio P, Morse B, Levy JB, Laforgia S, Huebner K. "Identification of a carbonic anhydrase-like domain in the extracellular region of RPTP gamma defines a new subfamily of receptor tyrosine phosphatases." Molecular and Cellular Biology, vol. 13, no. 3, 1993, pp. 1497-506

Levy JB, Canoll PD, Silvennoinen O, Barnea G, Morse B, Honegger AM, Huang JT, Cannizzaro LA, Park SH, Druck T. "The cloning of a receptor-type protein tyrosine phosphatase expressed in the central nervous system." Journal of Biological Chemistry, vol. 268, no. 14, 1993, pp. 10573-81.

Canoll PD, Barnea G, Levy JB, Sap J, Ehrlich M, Silvennoinen O, Schlessinger J, Musacchio JM. "The expression of a novel receptor-type tyrosine phosphatase suggests a role in morphogenesis and plasticity of the nervous system." Brain research. Developmental brain research, vol. 75, no. 2, 1993, pp. 293-8.

LaForgia S, Morse B, Levy J, Barnea G, Cannizzaro LA, Li F, Nowell PC, Boghosian-Sell L, Glick J, Weston A. "Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21." Proceedings of the National Academy of Sciences, vol. 88, no. 11, 1991, pp. 5036-40.

2008 – Pew Scholar in the Biomedical Sciences

2009 – Kavli Fellow, National Academy of Science

2009  NIH-EUREKA

2012  Robert and Nancy Carney Assistant Professor of Neuroscience

2014  NIH-EUREKA

2014  Brown Institute for Brain Science (BIBS) Innovation Award

2015  BIBS Innovation Award, Brown Institute for Brain Science

2016  Visiting Scientist, École des Neurosciences de Paris Île-de-France (ENP)

2017  The Pew Innovation Fund Award, The Pew charitable trusts

2018  Sidney A. Fox and Dorothea Doctors Fox Professor of Ophthalmology, Visual Sciences, and Neuroscience

Society for Neuroscience

Association for Chemoreception Sciences (AChemS)

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.