Chemical targeting of voltage sensitive dyes to specific cells and molecules in the brain Tomas Fiala1,||, Jihang Wang1,||, Matthew Dunn1, Peter Šebej1,12, Se Joon Choi3, Ekeoma C. Nwadibia1, Eva Fialova1, Diana M. Martinez,4 Claire E. Cheetham7, Keri J. Fogle8,9, Michael J. Palladino8,9 , Zachary Freyberg10,11, David Sulzer3,4,5,6* and Dalibor Sames1,2* 1Department of Chemistry, Columbia University, New York, NY, USA. 2NeuroTechnology Center at Columbia University, New York, NY, USA 3Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA. 4Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA. 5Department of Pharmacology, Columbia University Irving Medical Center, New York, NY, USA. 6Department of Molecular Therapeutics, New York Psychiatric Institute, New York, NY, USA. 7Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA. 8Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA. 9Pittsburgh Institute of Neurodegenerative Diseases (PIND), University of Pittsburgh, Pittsburgh, PA, USA. 10Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA. 11Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA. 12Current address: RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic. *Correspondence should be addressed to D. Sames (
[email protected]) or D. Sulzer (
[email protected]). 1 Graphical abstract: 2 Abstract Voltage sensitive fluorescent dyes (VSDs) are important tools for probing signal transduction in neurons and other excitable cells. These sensors, rendered highly lipophilic to anchor the conjugated -wire molecular framework in the membrane, offer several favorable functional parameters including fast response kinetics and high sensitivity to membrane potential changes. The impact of VSDs has, however, been limited due to the lack of cell-specific targeting methods in brain tissue or living animals.