DEPARTMENT OF NEUROBIOLOGY

Specializations

Regions(s): Systems Neuroscience; Brain and Behavior; Developmental Neuroscience; Cellular and Molecular Neuroscience

Research interest(s): Synaptic and Circuit Development in the Basal Ganglia

Research Summary

The Kozorovitskiy lab focuses on two broad, inter-related themes: decoding neuromodulation and neural circuit design principles. We seek to address the following questions:

• What activity-dependent rules govern the design of neural circuits and synapses in early life?
• How are these rules updated by experience and broken in disease?
• What is the function of neuromodulation during development and in behavior?   
• How do multiplexed neuromodulatory systems operate?

We investigate these questions primarily, but not exclusively, in the basal ganglia, a phylogenetically ancient region of the brain essential for complex, goal directed motor actions and reward-based behavior. One of our primary current interests is the influence of neurotransmitters, such as glutamate, GABA and dopamine, on synaptic development and neural circuit integration. To address these questions, we rely on 2-photon imaging and 2-photon neurotransmitter photorelease, whole-cell electrophysiology, opto- and pharmacogenetics, neuroanatomy, computational and behavioral analyses. We develop new rapid 3D fluorescence imaging modalities to facilitate neurobiological discoveries. 

Selected Publications

• Wu M, Minkowicz S, Dumrongprechachan V, Hamilton P, Kozorovitskiy Y (2021). Ketamine rapidly enhances glutamate-evoked dendritic spinogenesis in medial prefrontal cortex through dopaminergic mechanisms. Biological Psychiatry.
• Kumar, M, Kozorovitskiy, Y (2020). Tilt (in) variant lateral scan in oblique plane microscopy: a geometrical optics approach. Biomedical Optics Express, 11 (6), 3346-3359.
• Shmetov, A, Monakhov, M, Zhang, Q, Canton-Josh, J, Kumar, M, Chen, M, Matlashov, M, Li, X, Yang, W, Nie, L, Shcherbakova, D, Kozorivitskiy, Y, Yao, J, Ji, N, Verkhusha, V (2020). A near-infrared genetically encoded calcium indicator for in vivo imaging. Nature Biotechnology, 1-10. 
• Chen, C, Soto, G, Dumrongprechachan, V, Bannon, N, Kang, S, Kozorovitskiy, Y, Parisiadou, L (2020). Pathway-specific dysregulation of striatal excitatory synapses by LRRK2 mutations. Elife 9, e58997. 
• Kumar, M, Kozorovitskiy, Y (2019). Tilt-invariant scanned oblique plane illumination microscopy for large-scale volumetric imaging. Optics Letters, 44(7): 1706-1709.
• Kumar, M, Kishore, S, Nasenbeny, J, McLean, D, Kozorovitskiy, Y (2018). Integrated one-and two-photon scanned oblique plane illumination (SOPi) microscopy for rapid volumetric imaging. Optics Express.
• Xiao, L, Priest, MF, Kozorovitskiy, Y (2018). Oxytocin functions as a spatiotemporal filter for excitatory synaptic inputs to VTA dopamine neurons. eLife, 7, pii: e33892.
• Banala*, S, Arvin*, MC, Bannon, NM, Jin, XT, Macklin, JJ, Wang, Y, Peng, C, Zhao, G, Marshall, JJ, Gee, K, Wokosin, D, Kim, VJ, McIntosh, JM, Contractor, A, Lester, HA, Kozorovitskiy Y, Drenan, RM#, Lavis, LD# (2018). Development of photoactivatable drugs enables nicotinic optopharmacology. Nature Methods, 15(5):347-350.  
• Urban, B, Xiao, L, Chen, S, Yang, H, Dong, B, Kozorovitskiy, Y, Zhang, H. (2018). In vivo super-resolution imaging of neuronal structure in the mouse brain. IEEE Transactions on Biomedical Engineering, 65(1):232-238.
• Urban, B, Xiao L, Dong B, Chen S, Kozorovitskiy Y#, Zhang HF# (2018). Imaging neuronal structure dynamics using 2-photon super-resolution patterned excitation reconstruction microscopy. Journal of Biophotonics, 11(3).
• Xiao, L, Priest, MF, Nasenbeny, J, Lu, T, Kozorovitskiy, Y (2017). Biased Oxytocinergic Modulation of Midbrain Dopamine Systems. Neuron, 95(2):368-384.
• Peixoto, RT, Wang, W, Croney, DM, Kozorovitskiy, Y, Sabatini, BL (2016). Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B-/- mice. Nature Neuroscience, 19(5):716-724.
• Kozorovitskiy, Y, Peixoto, R, Wang, W, Saunders, A, Sabatini, B (2015).  Neuromodulation of excitatory synaptogenesis in striatal development. eLife, 4, pii: e10111.
  
• Tang J, Szikra T, Kozorovitskiy Y, Teixiera M, Sabatini B, Roska B, Cepko C. (2013). A nanobody-based system using fluorescent proteins as scaffolds for cell-specific gene manipulation. Cell, 154(4): 928-39.
• Kwon, H, Kozorovitskiy, Y, Oh, W, Peixoto, R, Akhtar, N, Saulnier, J, Gu, C, Sabatini, B. (2012). Neuroligin-1–dependent competition regulates cortical synaptogenesis and synapse number. Nat Neurosci, 15(12):1667-74.
• Kozorovitskiy, Y*, Saunders, A*, Johnson, C, Lowell, B, Sabatini, B. (2012). Recurrent network activity drives striatal synaptogenesis. Nature, 485(7400): 646-50.

Selected Honors/Awards

• 2019      NSF CAREER Award
• 2016      Searle Scholar Award, Kinship Foundation
• 2016      Sloan Research Fellowship, Alfred P. Sloan Foundation
• 2015      Cornew Innovation Award, Chemistry of Life Processes Institute
• 2015      Beckman Young Investigator Award, Arnold & Mabel Beckman Foundation
• 2015      Rita Allen Scholar Award, Rita Allen Foundation
  
• 2015      Whitehall Foundation Grant
• 2015      Early Career Investigators Innovation Award, William N. and Bernice E. Bumpus Foundation
• 2015      NARSAD Young Investigator Grant, Brain and Behavior Research Foundation
• 2014      Searle Leadership Fund Award, Northwestern University
• 2013      Anuradha Rao Memorial Award, Society for Neuroscience
• 2008      William F. Milton Fund Award, Harvard Medical School
• 2007      Junior Fellowship, Harvard University Society of Fellows