Maria Bykhovskaia, PhD
Maria Bykhovskaia, PhD
Dr. Bykhovskaia is a tenured Professor at the Department of neurology at Wayne State University School of Medicine. Her lab has expertise in cellular, molecular, and computational neuroscience, and the research program in the lab is focused on fundamental mechanistic problems in synaptic transmission. Her Ph.D. training was in computational biophysics and molecular modeling. Subsequently, she used a postdoc in neuroscience to initiate a career devoted to the study of presynaptic mechanisms and plasticity. As a PI, she developed in her lab the expertise in electrophysiology, live confocal imaging, and electron microscopy, and these experimental approaches are combined with mathematical and computational modeling. The research in the lab has been continuously supported by the National Institute of Health and the National Science Foundation. She has served as a member of review panels at the National Institute of health, the National Science Foundation, and the National Academy of Sciences.
Our research is focused on molecular machinery that controls the release of neuronal transmitters and from nerve terminals. Neuronal transmitters are packaged into synaptic vesicles and released by fusion of the vesicles with the neuronal membrane. We study the mobilization, docking and fusion of synaptic vesicles. These processes are highly dynamic and plastic, and disruptions in their regulation can produce severe neurological disorders, such as epilepsy, autism, Alzheimer’s and Huntington’s diseases, and mental retardation.
We employ genetically modified mice to investigate the role of vesicle associated protein synapsin. Since synapsin deficiency produces epilepsy in animal models and in humans, we employ genetic, electrophysiology, and molecular biology approaches to unravel the molecular and cellular pathways, which allow the synapsin proteins to control excitability in neuronal networks in the brain.
Another line of our research addresses a fundamental problem of structural synaptic plasticity. Intense neuronal activity can lead to the structural modifications of neuronal connections, and this phenomenon is thought to underlie the processes of learning and memory. We use Drosophila neuromuscular junctions to study the activity-dependent modifications in neuronal connections, since this model organism provides excellent opportunities for creating genetically modified animals and observing neuronal growth and differentiation in a real time.
Recently, we focused on the question of how the fusion molecular machinery regulates the latest stages of the fusion of synaptic vesicles with the neuronal membrane. We combine molecular modeling, Drosophila genetics, and electrophysiology, aiming to develop computational tools, which would allow us to manipulate the fusion machinery via targeted mutagenesis.
Leningrad Polytechnic University M.S. 1987 Biophysics
Sechenov Institute of Evolutionary Physiology Ph.D. 1992 Computational Biophysics
Professor of Neurology and Anatomy
University of Virginia PostDoc 1997 Neuroscience
1. Vasin A, Sabeva N, Torres C, Phan S, Bushong EA, Ellisman MH, Bykhovskaia M. 2019. Two Pathways for the Activity-Dependent Growth and Differentiation of Synaptic Boutons in Drosophila. eNeuro. 2019 6(4). pii: ENEURO.0060-19.2019.
2. Matos H, Quiles R, Andrade R, Bykhovskaia M.2019. Growth and excitability at synapsin II deficient hippocampal neurons. Mol Cell Neurosci. 96:25-34.
3. Bykhovskaia M. 2019. Molecular Dynamics Simulations of the SNARE Complex. Methods Mol Biol. 1860:3- 13.
4. Fortoul N, Bykhovskaia M, Jagota A. 2018. Coarse-Grained Model for Zippering of SNARE from partially Assembled States. J. Phys. Chem. 6;122(48):10834-10840.
5. Sabeva NS, Bykhovskaia M. 2017 FM1-43 Photoconversion and Electron Microscopy
Analysis at the Drosophila Neuromuscular Junction. Bio Protoc. pii: e2523.
6. Bykhovskaia M, Vasin A. 2017. Electrophysiological analysis of synaptic transmission in Drosophila. Wiley Interdiscip Rev Dev Biol. doi: 10. 1002/wdev 277.
7. Vasin A, Bykhovskaia M. 2017. Focal Macropatch Recordings of Synaptic Currents from the Drosophila Larval Neuromuscular Junction. J Vis Exp. doi: 10.3791/56493.
8. Feliciano P., H. Matos, R. Andrade, and M. Bykhovskaia. 2017. Synapsin II regulation of GABAergic synaptic transmission is dependent on interneuron subtype. J. Neurosci. 15;37(7):1757-1771.
9. Sabeva N., Cho. R., Vasin, A. Gonzalez, J.T. Littleton, and M. Bykhovskaia. (2017) Complexin Mutants Reveal Partial Segregation Between Recycling Pathways that Drive Evoked and Spontaneous Neurotransmission J Neurosci 3:383-396.
10. Guan Z, Bykhovskaia M, Jorquera RA, Sutton RB, Akbergenova Y, Littleton JT. (2017) A synaptotagmin suppressor screen indicates SNARE binding controls the timing and Ca(2+) cooperativity of vesicle fusion. Elife. pii: e28409.
11. Michaeli L, Gottfried I, Bykhovskaia M, Ashery U. (2017) Phosphatidylinositol (4,5)-bisphosphate targets double C2 domain protein B to the plasma membrane. Traffic. 18:825-39.
12. Vasin, A., Volfson, D., Littleton, J. T., and Bykhovskaia, M. (2016) Interaction of the Complexin Accessory Helix with Synaptobrevin Regulates Spontaneous Fusion, Biophys J 111, 1954-1964.
13. Bykhovskaia M. 2015. Calcium binding promotes conformational flexibility of the neuronal Ca2+ sensor synaptotagmin. Biophys. J. 108:2507-20.
14. Fortoul, N., Singh P., Hui C.Y., Bykhovskaia M., and A. Jagota. 2015. Coarse-Grained Model of the Snare Complex Determines the Number of Snares Required for Docking. Biophys. J. 108:2258-69.
15. Vasin A., L. Zueva, C.Torrez, D.Volfson, J.T.Littleton, and M.Bykhovskaia. 2014. Synapsin regulates activity-dependent outgrowth of synaptic boutons at the Drosophila neuromuscular junction. J. Neurosci. 34:10554:63.
16. Feliciano P., R. Andrade, and M. Bykhovskaia. 2013. Synapsin II and Rab3a cooperate in the regulation of epileptic and synaptic activity at in the CA1 region of the hippocampus synapses. J. Neurosci. 33:18319-30.
17. Bykhovskaia M., A. Jagota, A. Gonzales, A. Vasin, and J.T. Littleton. 2013. Interaction of the complexin accessory helix with the C-terminus of the SNARE complex: molecular dynamics model of the fusion clamp. Biophys. J. 105:679-90.
18. Bykhovskaia M. 2011. Synapsin regulation of vesicle organization and functional pools. Semin. Cell Dev. Biol. 22(4):387-92.
19. Akbergenova Y, Bykhovskaia M. 2009. Stimulation-induced formation of the reserve pool of vesicles in Drosophila motor boutons. J Neurophysiol 101: 2423-2433.
20. Coleman WL, Bill CA, Simsek-Duran F, Lonart G, Samigullin D, Bykhovskaia M. 2008. Synapsin II and calcium regulate vesicle docking and the cross-talk between vesicle pools at the mouse motor terminals. J Physiol 586: 4649-4673.