Novel implantable imaging system for enabling simultaneous multiplanar and multipoint analysis for fluorescence potentiometry in the visual cortex.

Techniques for fast, noninvasive measurement of neuronal excitability within a broad area will be of major importance for analyzing and understanding neuronal networks and animal behavior in neuroscience field. In this research, a novel implantable imaging system for fluorescence potentiometry was developed using a complementary metal-oxide semiconductor (CMOS) technology, and its application to the analysis of cultured brain slices and the brain of a living mouse is described. A CMOS image sensor, small enough to be implanted into the brain, with light-emitting diodes and an absorbing filter was developed to enable real-time fluorescence imaging. The sensor, in conjunction with a voltage-sensitive dye, was certainly able to visualize the potential statuses of neurons and obtain physiological responses in both right and left visual cortex simultaneously by using multiple sensors for the first time. This accomplished multiplanar and multipoint measurement provides multidimensional information from different aspects. The light microsensors do not disturb the animal behavior. This implies that the imaging system can combine functional fluorescence imaging in the brain with behavioral experiments in a freely moving animal.

[1]  E. Hillman,et al.  Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics. , 2009, Optics express.

[2]  Eugenio Culurciello,et al.  Head-mountable high speed camera for optical neural recording , 2011, Journal of Neuroscience Methods.

[3]  D. Tank,et al.  A Miniature Head-Mounted Two-Photon Microscope High-Resolution Brain Imaging in Freely Moving Animals , 2001, Neuron.

[4]  Michael P. Stryker,et al.  New Paradigm for Optical Imaging Temporally Encoded Maps of Intrinsic Signal , 2003, Neuron.

[5]  Amiram Grinvald,et al.  VSDI: a new era in functional imaging of cortical dynamics , 2004, Nature Reviews Neuroscience.

[6]  Katsuei Shibuki,et al.  Enduring Critical Period Plasticity Visualized by Transcranial Flavoprotein Imaging in Mouse Primary Visual Cortex , 2006, The Journal of Neuroscience.

[7]  Stanislav Herwik,et al.  A Wireless Multi-Channel Recording System for Freely Behaving Mice and Rats , 2011, PloS one.

[8]  Jun Ohta,et al.  Potentiometric Dye Imaging for Pheochromocytoma and Cortical Neurons with a Novel Measurement System Using an Integrated Complementary Metal–Oxide–Semiconductor Imaging Device , 2010 .

[9]  E.R. Fossum,et al.  256/spl times/256 CMOS active pixel sensor camera-on-a-chip , 1996, 1996 IEEE International Solid-State Circuits Conference. Digest of TEchnical Papers, ISSCC.

[10]  Arjun G Yodh,et al.  Two-photon excitation of potentiometric probes enables optical recording of action potentials from mammalian nerve terminals in situ. , 2008, Journal of neurophysiology.

[11]  John L. Crassidis,et al.  Sensors and actuators , 2005, Conference on Electron Devices, 2005 Spanish.

[12]  Masa-aki Sato,et al.  Visual Image Reconstruction from Human Brain Activity using a Combination of Multiscale Local Image Decoders , 2008, Neuron.

[13]  B. Salzberg,et al.  Optical Recording of Impulses in Individual Neurones of an Invertebrate Central Nervous System , 1973, Nature.

[14]  Jun Ohta,et al.  Complementary Metal-Oxide-Semiconductor Image Sensor with Microchamber Array for Fluorescent Bead Counting , 2012 .

[15]  R. Keynes,et al.  Light Scattering and Birefringence Changes during Nerve Activity , 1968, Nature.

[16]  Jun Ohta,et al.  Multimodal Complementary Metal–Oxide–Semiconductor Sensor Device for Imaging of Fluorescence and Electrical Potential in Deep Brain of Mouse , 2010 .

[17]  Masahiro Nunoshita,et al.  Real time in vivo imaging and measurement of serine protease activity in the mouse hippocampus using a dedicated complementary metal-oxide semiconductor imaging device , 2006, Journal of Neuroscience Methods.

[18]  V. Sossi,et al.  Micropet imaging: in vivo biochemistry in small animals , 2005, Journal of Neural Transmission.

[19]  K. Yasuda,et al.  Generation of a second eye by embryonic transplantation of the antero‐ventral hemicephalon , 2009, Development, growth & differentiation.

[20]  K. Shibuki,et al.  Transcranial electrical stimulation of cortico-cortical connections in anesthetized mice , 2011, Journal of Neuroscience Methods.

[21]  A Watanabe,et al.  Changes in fluorescence, turbidity, and birefringence associated with nerve excitation. , 1968, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Jiro Suzuki,et al.  Epileptic seizure of El mouse initiates at the parietal cortex: depth EEG observation in freely moving condition using buffer amplifier , 1993, Brain Research.

[23]  A. Grinvald,et al.  Optical methods for monitoring neuron activity. , 1978, Annual review of neuroscience.

[24]  D. Coulter,et al.  In vitro functional imaging in brain slices using fast voltage-sensitive dye imaging combined with whole-cell patch recording , 2008, Nature Protocols.

[25]  H. Kadono,et al.  Novel functional imaging technique from brain surface with optical coherence tomography enabling visualization of depth resolved functional structure in vivo , 2003, Journal of Neuroscience Methods.

[26]  T. Wiesel,et al.  Functional architecture of cortex revealed by optical imaging of intrinsic signals , 1986, Nature.

[27]  Patrick O Kanold,et al.  Multiple periods of functional ocular dominance plasticity in mouse visual cortex , 2005, Nature Neuroscience.

[28]  B. Salzberg,et al.  Novel naphthylstyryl-pyridinium potentiometric dyes offer advantages for neural network analysis , 2004, Journal of Neuroscience Methods.

[29]  Michael P. Stryker,et al.  Anatomical Correlates of Functional Plasticity in Mouse Visual Cortex , 1999, The Journal of Neuroscience.

[30]  Chin-Teng Lin,et al.  Imaging brain hemodynamic changes during rat forepaw electrical stimulation using functional photoacoustic microscopy , 2010, NeuroImage.

[31]  R. Frostig,et al.  Cortical point-spread function and long-range lateral interactions revealed by real-time optical imaging of macaque monkey primary visual cortex , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  Jun Ohta,et al.  One-chip sensing device (biomedical photonic LSI) enabled to assess hippocampal steep and gradual up-regulated proteolytic activities , 2008, Journal of Neuroscience Methods.

[33]  Jun Ohta,et al.  Implantable CMOS Biomedical Devices , 2009, Sensors.

[34]  K. Yasuda,et al.  Coordinated regulation of dorsal bone morphogenetic protein 4 and ventral Sonic hedgehog signaling specifies the dorso‐ventral polarity in the optic vesicle and governs ocular morphogenesis through fibroblast growth factor 8 upregulation , 2010, Development, growth & differentiation.

[35]  Jun Ohta,et al.  CMOS image sensor integrated with micro-LED and multielectrode arrays for the patterned photostimulation and multichannel recording of neuronal tissue. , 2012, Optics express.

[36]  Uma Maheswari Rajagopalan,et al.  Functional optical coherence tomography reveals localized layer-specific activations in cat primary visual cortex in vivo. , 2007, Optics letters.

[37]  Jun Ohta,et al.  CMOS Imaging Devices for Biomedical Applications , 2011, IEICE Trans. Commun..

[38]  J. Pratte,et al.  Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph , 2011, Nature Methods.

[39]  Masahiro Nunoshita,et al.  An implantable and fully integrated complementary metal–oxide semiconductor device for in vivo neural imaging and electrical interfacing with the mouse hippocampus , 2008 .

[40]  B M Salzberg,et al.  A large change in axon fluorescence that provides a promising method for measuring membrane potential. , 1973, Nature: New biology.

[41]  Konrad Lehmann,et al.  Vision and visual cortical maps in mice with a photoreceptor synaptopathy: Reduced but robust visual capabilities in the absence of synaptic ribbons , 2010, NeuroImage.