Delivered by Publishing Technology to: Editor in Chief IP: 137.132.250.14 On: Thu, 06 Mar 2014 10:07:09 Copyright: American Scientific Publishers Copyright © 2014 American Scientific Publishers All rights reserved Printed in the United States of America Review Journal of Nanoscience and Nanotechnology Vol. 14, 4733–4744, 2014 www.aspbs.com/jnn Recent Progress in Voltage-Sensitive Dye Imaging for Neuroscience Vassiliy Tsytsarev 1 *† , Lun-De Liao 2† , Kien Voon Kong 3 , Yu-Hang Liu 2 , Reha S. Erzurumlu 1 , Malini Olivo 3 5 , and Nitish V. Thakor 2 4 1 Department of Anatomy and Neurobiology, University of Maryland School of Medicine, HSF-2, Baltimore, MD 21201, USA 2 Singapore Institute for Neurotechnology (SINAPSE), National University of Singapore, 28 Medical Drive, #05-COR, Singapore 117456 3 Singapore Bioimaging Consortium, Agency for Science, Technology and Research, 138667, Singapore 4 Department of Biomedical Engineering, Johns Hopkins University, Traylor 701/720 Rutland Ave, Baltimore, MD 21205, USA 5 School of Physics, National University of Ireland, Galway, Ireland Voltage-sensitive dye imaging (VSDi) enables visualization of information processing in different areas of the brain with reasonable spatial and temporal resolution. VSDi employs different chemical compounds to transduce neural activity directly into the changes in intrinsic optical signal. Physi- cally, voltage-sensitive dyes (VSDs) are chemical probes that reside in the neural membrane and change their fluorescence or absorbance in response to membrane potential changes. Based on these features, VSDs can be divided into two groups-absorbance and fluorescence. The spatial and temporal resolution of the VSDi is limited mainly by the technical characteristics of the optical imaging setup (e.g., computer and light-sensitive device-charge-coupled device (CCD) camera or photodiode array). In this article, we briefly review the development of the VSD, technique of VSDi and applications in functional brain imaging. Keywords: Brain Imaging, Contrast Agents, Functional Brain Mapping, Functional Brain Imaging, Optical Imaging, Voltage-Sensitive Dye Imaging. CONTENTS 1. Introduction ........................................ 4733 2. Basic Mechanisms of VSDi ............................ 4735 3. Physico-Chemical Basis of VSD ........................ 4736 4. VSDi in Neuroscience ................................ 4739 5. Conclusions ........................................ 4741 References and Notes ................................ 4741 1. INTRODUCTION Visualization of the neural activity in vivo is an important objective in both fundamental and clinical neuroscience. There are now several optical imaging methods, based on the changes of the optical properties of the brain tis- sue that can be used to measure neural activity. These include intrinsic signal optical imaging, near-infrared * Author to whom correspondence should be addressed. † These two authors contributed equally to this work. optical imaging, functional photoacoustic tomography, optical coherence tomography and optical imaging with voltage sensitive dyes (VSDi). Here, we review a wide variety of VSDi approaches for the study of neural activ- ities in the brain. Optical techniques enabling the descrip- tion of brain function at levels ranging from single cells to neural ensembles are also introduced in this article. Understanding cortical function after neural activation allows probing into cerebral neurovascular coupling and uncoupling functions. 1 To date, many neuroimaging tech- niques are available to provide the information of neural circuit functions in both laboratory animals and humans. 1 VSDi is a powerful technique for studying neural circuit functions with relatively high spatial (up to 20 m) and temporal (up to tens of microseconds) resolution, compa- rable to electrophysiology techniques. 2 3 The first optical recordings of membrane potentials using VSDi were done more than three decades ago on the squid giant axon and in J. Nanosci. Nanotechnol. 2014, Vol. 14, No. 7 1533-4880/2014/14/4733/012 doi:10.1166/jnn.2014.9531 4733