Jay Hirsh | University of Virginia School of Medicine

Bio & Overview

My laboratory is using the fruit fly, Drosophila melanogaster, as a model system for studying the molecular genetics of responsiveness to cocaine and other drugs of abuse. We have shown that exposure to aerosolized free base cocaine induces multiple reflexive motor responses that resemble cocaine induced behaviors in vertebrates, and also resemble dopamine agonist induced behaviors previously observed in decapitated flies (Yellman et al, 1997). Furthermore, Drosophila develop behavioral sensitization to intermittent doses of cocaine. Sensitization has been linked to the addictive processes in vertebrates, and it is of great interest to understand the basic mechanisms leading to sensitization in a simple model system. Our results suggest that the pathways leading to cocaine induced responses are evolutionarily conserved between Drosophila and higher vertebrates, and that this genetically tractable animal can be used as a new model system to help determine the biological mechanisms underlying these processes. Recent studies are uncovering some unexpected gene products and small molecules involved in sensitization in flies. We have found that regulated production of the trace amine tyramine is essential for the development of sensitization (McClung & Hirsh, 1999). In addition, we have found that a subset of genes essential for fly circadian functions are required for sensitization (Andretic et al, 1999). Given the conservation of structure and function of these circadian genes in animals from flies to higher vertebrates, there is a strong likelihood of conserved functions for these genes in modulating drug responses across evolution. Ongoing studies are aimed at further elucidating the mechanisms and genes involved in modulating sensitization and drug responsiveness. PLEASE NOTE: Funded Postdoctoral position available to work on the above studies. Contact Jay for further information.

Academic Information

Department: Biology

Academic Title: Professor

Primary Education

BA, Chemistry, Northwestern University, 1971
PhD, Biochemistry, Brandeis University, 1976

Other Appointments

Professor, Neuroscience
Professor, MCDB

Other Affiliations

Professor, BIMS

Research Interests

Molecular genetics; development and function of neurotransmitter-synthesizing neurons in Drosophila

Research Disciplines

Neuroscience

Research Opportunities

Neuroscience

Selected Publications

2019

Sangston, R., & Hirsh, J. (2019). An inexpensive air stream temperature controller and its use to facilitate temperature-controlled behavior in Drosophila. BIOTECHNIQUES, 66(3), 159-161. doi:10.2144/btn-2018-0152

2018

Friedman, D. A., Pilko, A., Skowronska-Krawczyk, D., Krasinska, K., Parker, J. W., Hirsh, J., & Gordon, D. M. (2018). The Role of Dopamine in the Collective Regulation of Foraging in Harvester Ants. ISCIENCE, 8, 283-+. doi:10.1016/j.isci.2018.09.001

Cichewicz, K., & Hirsh, J. (2018). ShinyR-DAM: a program analyzing Drosophila activity, sleep and circadian rhythms. COMMUNICATIONS BIOLOGY, 1. doi:10.1038/s42003-018-0031-9

2017

Mead, B. P., Kim, N., Miller, G. W., Hodges, D., Mastorakos, P., Klibanov, A. L., . . . Price, R. J. (2017). Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores Dopaminergic Neuron Function in a Rat Parkinson's Disease Model. NANO LETTERS, 17(6), 3533-3542. doi:10.1021/acs.nanolett.7b00616

Sipe, L. M., Yang, C., Ephrem, J., Garren, E., Hirsh, J., & Deppmann, C. D. (2017). Differential sympathetic outflow to adipose depots is required for visceral fat loss in response to calorie restriction. NUTRITION & DIABETES, 7. doi:10.1038/nutd.2017.13

Niens, J., Reh, F., Coban, B., Cichewicz, K., Eckardt, J., Liu, Y. -T., . . . Riemensperger, T. D. (2017). Dopamine Modulates Serotonin Innervation in the Drosophila Brain. FRONTIERS IN SYSTEMS NEUROSCIENCE, 11. doi:10.3389/fnsys.2017.00076

2016

Cichewicz, K., Garren, E. J., Adiele, C., Aso, Y., Wang, Z., Wu, M., . . . Hirsh, J. (2017). A new brain dopamine-deficient Drosophila and its pharmacological and genetic rescue. GENES BRAIN AND BEHAVIOR, 16(3), 394-403. doi:10.1111/gbb.12353

Nall, A. H., Shakhmantsir, I., Cichewicz, K., Birman, S., Hirsh, J., & Sehgal, A. (2016). Caffeine promotes wakefulness via dopamine signaling in Drosophila. SCIENTIFIC REPORTS, 6. doi:10.1038/srep20938

2013

Vinayak, P., Coupar, J., Hughes, S. E., Fozdar, P., Kilby, J., Garren, E., . . . Hirsh, J. (2013). Exquisite Light Sensitivity of Drosophila melanogaster Cryptochrome. PLOS GENETICS, 9(7). doi:10.1371/journal.pgen.1003615

2012

Hirsh, J. (2012). Bill Pak, Neurobiology, ninaE, and Me. JOURNAL OF NEUROGENETICS, 26(2), 168-176. doi:10.3109/01677063.2012.700347

Kistenpfennig, C., Hirsh, J., Yoshii, T., & Helfrich-Foerster, C. (2012). Phase-Shifting the Fruit Fly Clock without Cryptochrome. JOURNAL OF BIOLOGICAL RHYTHMS, 27(2), 117-125. doi:10.1177/0748730411434390

2011

Lee, P. -T., Lin, H. -W., Chang, Y. -H., Fu, T. -F., Dubnau, J., Hirsh, J., . . . Chiang, A. -S. (2011). Serotonin-mushroom body circuit modulating the formation of anesthesia-resistant memory in Drosophila. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108(33), 13794-13799. doi:10.1073/pnas.1019483108

Kaun, K. R., Azanchi, R., Maung, Z., Hirsh, J., & Heberlein, U. (2011). A Drosophila model for alcohol reward. NATURE NEUROSCIENCE, 14(5), 612-U103. doi:10.1038/nn.2805

2010

Riemensperger, T., Isabel, G., Coulom, H., Neuser, K., Seugnet, L., Kume, K., . . . Birman, S. (2011). Behavioral consequences of dopamine deficiency in the Drosophila central nervous system. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 108(2), 834-839. doi:10.1073/pnas.1010930108

Kong, E. C., Woo, K., Li, H., Lebestky, T., Mayer, N., Sniffen, M. R., . . . Wolf, F. W. (2010). A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila. PLOS ONE, 5(3). doi:10.1371/journal.pone.0009954

Zhao, Y., Bretz, C. A., Hawksworth, S. A., Hirsh, J., & Johnson, E. C. (2010). Corazonin Neurons Function in Sexually Dimorphic Circuitry That Shape Behavioral Responses to Stress in Drosophila. PLOS ONE, 5(2). doi:10.1371/journal.pone.0009141

Hirsh, J., Riemensperger, T., Coulom, H., Iche, M., Coupar, J., & Birman, S. (2010). Roles of Dopamine in Circadian Rhythmicity and Extreme Light Sensitivity of Circadian Entrainment. CURRENT BIOLOGY, 20(3), 209-214. doi:10.1016/j.cub.2009.11.037