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1111
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
DESIGN, DEVELOPMENT AND PACKAGING OF AN
OPTRODE FOR NEURONAL APPLICATIONSOPTRODE FOR NEURONAL APPLICATIONS
Rabinder Henry
2222
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
Introduction
Optogenetic Tool
CONTENTS
Analyses
Future perspective
3333
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
OPTOGENETICS
Optics Genetics
Optogenetics
Selective control of neuronal activity using light -photoexcitation /photoinhibition
Millisecond-scale temporal precision -gain or loss of function of precise events
Microbial opsin genes - optical control of action potential patterns
Deisseroth, K., Feng, G., Majewska, A.K., Miesenbo¨ ck, G., Ting, A., and Schnitzer, M.J. (2006). Next-generation optical
technologies for illuminating genetically targeted brain circuits. J. Neurosci. 26, 10380–10386.
4444
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
Recording Electrode
Neural resposne recording
Light Emitting Structure
Photostimulation of specific cells
Optrode
OPTOGENETIC TOOL
Genetically Modified Light Sensitive Channels
Optrode
OPTOGENETIC TOOLNon-selective activation of cells
Multipath Current flow
Artifacts interference
Excitation and inhibtion
Minimal interference
Scalable Process to deeper parts
5555
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
Genetically Modified Light Sensitive Channels
Fast light-activated channels and enzymes
Temporally precise manipulation of electrical and biochemical events
Microbial Opsins (rhodopsin)
Visual proteins - unicellular algae, bacteria and archaebacteria
7-transmembrane (TM) rhodopsins
Photoreceptors
Optimal intensity location
(photosynthesis)
Figure 1:7-Transmembrane (TM) rhodopsins
(photosynthesis)
6666
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
Investigate the function of neural systems
Non-lightsensitive cells to enable rapid optical control
Channelrhodopsin-2 (ChR2) ,λ=480 nm (Blue )
Cation channels, conducting H+, Na+, K+, Ca2+
Light absorption Retinal
isomerization
Gating Thermal
relaxation
Closing
Figure 2: Channelrhodopsin
Retinal-Vitamin A derivative
Mammalian Neuronal Cells
Generation of hybrids ChRs
spectral and kinetic properties
Improve expression in host
7777
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
JingWang Integrated device for combined optical neuromodulation and electrical recording
for chronic in vivo applications, Journal of Neural Engineering .
CURRENT PERSPECTIVE
Figure 4:Waveguide based Optrode
8888
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
Anthony N. Zorzos, Edward S. Boyden, and Clifton G. Fonstad, Multiwaveguide implantable probe for
light delivery to sets of distributed brain targets. Optical Soceity of America
CURRENT PERSPECTIVE
Figure 5:Micromirros based Optrode
9999
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
ANALYZES
Possible light-induced damage to neurons at the tip of the electrode
Possible photoinduced detrimental effects to the cells in the immediate vicinity
Limitations of using optical fiber based endoscopic technologies
Optical coupling between light sources and optical guides
Diffraction of electromagnetic radiation by a circular hole in an infinitely thin and
perfectly conducting screen
Tissue damage due to electrode tips
Optical inter -modulation
Temperature effects of optical source
10101010
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
FUTURE PERSPECTIVE
Polymer based microelectrodes with OLED – 3D structure
Polymer based microelectrodes with ILED
Nir Grossman .et .al ,Multi-site optical excitation using ChR2 and micro-LED array, 2009
Wireless, Ultra Low Power, Broadband Neural Recording Microsystem
Reference :http://nurmikko.engin.brown.edu/?q=node/1
Blue-Green and Ultraviolet micro-LEDs in Neural
Imaging and Stimulation
11111111
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
FUTURE PERSPECTIVE
Polymer based microelectrodes with OLED – 3D structure - ASIC
OLED
Wireless
Electrode
Photodiode
ASIC
Polymer
12121212
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
[1] Jiayi Zhang, Farah Laiwalla, Jennifer A Kim, Hayato Urabe, Rick VanWagenen, Yoon-Kyu Song,
BarryWConnors, Feng Zhang,Karl Deisseroth and Arto V Nurmikko, “ Integrated device for optical
stimulation and spatiotemporal electrical recording of neural activity in light-sensitized brain tissue, ”
Journal of Neural Engineering, Volume 6 ,IOP, 2009.
[2] JingWang, FabienWagner, David A Borton, Jiayi Zhang,Ilker Ozden, Rebecca D Burwell, Arto V
Nurmikko, Rick vanWagenen, Ilka Diester and Karl Deisseroth,“ Integrated device for combined optical
neuromodulation and electrical recording for chronic in vivo applications,” Journal of Neural
Engineering, Volume 9 ,IOP, 2012.
REFERENCES
Engineering, Volume 9 ,IOP, 2012.
[3] Matthew R. Banghart, Matthew Volgraf, and Dirk Trauner, “ Engineering Light-Gated Ion Channels,”
American Chemical Society, February ,2006.
[4] Polina Anikeeva, et .al,“ Optetrode: a multichannel readout for optogenetic control in freely moving
mice,” Nature Neuroscience ,volume 15 ,number 1, January 2012.
[5] http://nurmikko.engin.brown.edu/?q=node/46
[6] Feng Zhang et.al., “ The Microbial Opsin Family of Optogenetic Tools,” Cell Elsevier1,47,
December 23, 2011.
[7] http://www.openoptogenetics.org/index.php?title=Channelrhodopsins
13131313
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
But I have promises to keep !
And Miles to Go before I sleep !
And Miles to Go before I sleep !!
Robert Frost, 1922.Robert Frost, 1922.
14141414
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
Questions ?
Contact: Rabinder Henry
https://www.facebook.com/rabinder.henry
https://in.linkedin.com/in/rabinder-henry-02284aa
15151515
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
40
0
Membranepotential(mv)
Depolarization
Repolarization
Overshoot
- 70
- 90
Membranepotential(mv)
Time
Hyperpolarization
Depolarization
Repolarization
- 50
Positive (hyperpolarizing) afterpotential
Negative (depolarizing) afterpotential
Threshold
16161616
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
Presynaptic cell
+
+
+
+
-
-
-
+
+
+
+
+
+
-
-
-
-
-
-
Action zone
Postsynaptic cell
Electrical
events
Action
potential
Depolarization
Action
potentialSynaptic potential
+
+
+
+
+-
-
-
-
-
+
+
+
-
-
-
-
-
Neurotransmitter
released
Diffusion of
Neurotransmitter
Postsynaptic membrane
activation
Chemial
events
Neurotransmitter
receptor reaction
17171717
Institut für Mikro- und Sensorsysteme
Lehrstuhl Mikrosystemtechnik
Presynaptic cell
Postsynaptic cell
Neural vector Transgene transcription
Ion channel
Receptor
Neurotransmitter precursor
Transgene translation
Ion channel
Docking protein
Re-uptake protein
Second
messenger

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Optogenetics -Public presentation

  • 1. 1111 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik DESIGN, DEVELOPMENT AND PACKAGING OF AN OPTRODE FOR NEURONAL APPLICATIONSOPTRODE FOR NEURONAL APPLICATIONS Rabinder Henry
  • 2. 2222 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik Introduction Optogenetic Tool CONTENTS Analyses Future perspective
  • 3. 3333 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik OPTOGENETICS Optics Genetics Optogenetics Selective control of neuronal activity using light -photoexcitation /photoinhibition Millisecond-scale temporal precision -gain or loss of function of precise events Microbial opsin genes - optical control of action potential patterns Deisseroth, K., Feng, G., Majewska, A.K., Miesenbo¨ ck, G., Ting, A., and Schnitzer, M.J. (2006). Next-generation optical technologies for illuminating genetically targeted brain circuits. J. Neurosci. 26, 10380–10386.
  • 4. 4444 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik Recording Electrode Neural resposne recording Light Emitting Structure Photostimulation of specific cells Optrode OPTOGENETIC TOOL Genetically Modified Light Sensitive Channels Optrode OPTOGENETIC TOOLNon-selective activation of cells Multipath Current flow Artifacts interference Excitation and inhibtion Minimal interference Scalable Process to deeper parts
  • 5. 5555 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik Genetically Modified Light Sensitive Channels Fast light-activated channels and enzymes Temporally precise manipulation of electrical and biochemical events Microbial Opsins (rhodopsin) Visual proteins - unicellular algae, bacteria and archaebacteria 7-transmembrane (TM) rhodopsins Photoreceptors Optimal intensity location (photosynthesis) Figure 1:7-Transmembrane (TM) rhodopsins (photosynthesis)
  • 6. 6666 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik Investigate the function of neural systems Non-lightsensitive cells to enable rapid optical control Channelrhodopsin-2 (ChR2) ,λ=480 nm (Blue ) Cation channels, conducting H+, Na+, K+, Ca2+ Light absorption Retinal isomerization Gating Thermal relaxation Closing Figure 2: Channelrhodopsin Retinal-Vitamin A derivative Mammalian Neuronal Cells Generation of hybrids ChRs spectral and kinetic properties Improve expression in host
  • 7. 7777 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik JingWang Integrated device for combined optical neuromodulation and electrical recording for chronic in vivo applications, Journal of Neural Engineering . CURRENT PERSPECTIVE Figure 4:Waveguide based Optrode
  • 8. 8888 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik Anthony N. Zorzos, Edward S. Boyden, and Clifton G. Fonstad, Multiwaveguide implantable probe for light delivery to sets of distributed brain targets. Optical Soceity of America CURRENT PERSPECTIVE Figure 5:Micromirros based Optrode
  • 9. 9999 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik ANALYZES Possible light-induced damage to neurons at the tip of the electrode Possible photoinduced detrimental effects to the cells in the immediate vicinity Limitations of using optical fiber based endoscopic technologies Optical coupling between light sources and optical guides Diffraction of electromagnetic radiation by a circular hole in an infinitely thin and perfectly conducting screen Tissue damage due to electrode tips Optical inter -modulation Temperature effects of optical source
  • 10. 10101010 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik FUTURE PERSPECTIVE Polymer based microelectrodes with OLED – 3D structure Polymer based microelectrodes with ILED Nir Grossman .et .al ,Multi-site optical excitation using ChR2 and micro-LED array, 2009 Wireless, Ultra Low Power, Broadband Neural Recording Microsystem Reference :http://nurmikko.engin.brown.edu/?q=node/1 Blue-Green and Ultraviolet micro-LEDs in Neural Imaging and Stimulation
  • 11. 11111111 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik FUTURE PERSPECTIVE Polymer based microelectrodes with OLED – 3D structure - ASIC OLED Wireless Electrode Photodiode ASIC Polymer
  • 12. 12121212 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik [1] Jiayi Zhang, Farah Laiwalla, Jennifer A Kim, Hayato Urabe, Rick VanWagenen, Yoon-Kyu Song, BarryWConnors, Feng Zhang,Karl Deisseroth and Arto V Nurmikko, “ Integrated device for optical stimulation and spatiotemporal electrical recording of neural activity in light-sensitized brain tissue, ” Journal of Neural Engineering, Volume 6 ,IOP, 2009. [2] JingWang, FabienWagner, David A Borton, Jiayi Zhang,Ilker Ozden, Rebecca D Burwell, Arto V Nurmikko, Rick vanWagenen, Ilka Diester and Karl Deisseroth,“ Integrated device for combined optical neuromodulation and electrical recording for chronic in vivo applications,” Journal of Neural Engineering, Volume 9 ,IOP, 2012. REFERENCES Engineering, Volume 9 ,IOP, 2012. [3] Matthew R. Banghart, Matthew Volgraf, and Dirk Trauner, “ Engineering Light-Gated Ion Channels,” American Chemical Society, February ,2006. [4] Polina Anikeeva, et .al,“ Optetrode: a multichannel readout for optogenetic control in freely moving mice,” Nature Neuroscience ,volume 15 ,number 1, January 2012. [5] http://nurmikko.engin.brown.edu/?q=node/46 [6] Feng Zhang et.al., “ The Microbial Opsin Family of Optogenetic Tools,” Cell Elsevier1,47, December 23, 2011. [7] http://www.openoptogenetics.org/index.php?title=Channelrhodopsins
  • 13. 13131313 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik But I have promises to keep ! And Miles to Go before I sleep ! And Miles to Go before I sleep !! Robert Frost, 1922.Robert Frost, 1922.
  • 14. 14141414 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik Questions ? Contact: Rabinder Henry https://www.facebook.com/rabinder.henry https://in.linkedin.com/in/rabinder-henry-02284aa
  • 15. 15151515 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik 40 0 Membranepotential(mv) Depolarization Repolarization Overshoot - 70 - 90 Membranepotential(mv) Time Hyperpolarization Depolarization Repolarization - 50 Positive (hyperpolarizing) afterpotential Negative (depolarizing) afterpotential Threshold
  • 16. 16161616 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik Presynaptic cell + + + + - - - + + + + + + - - - - - - Action zone Postsynaptic cell Electrical events Action potential Depolarization Action potentialSynaptic potential + + + + +- - - - - + + + - - - - - Neurotransmitter released Diffusion of Neurotransmitter Postsynaptic membrane activation Chemial events Neurotransmitter receptor reaction
  • 17. 17171717 Institut für Mikro- und Sensorsysteme Lehrstuhl Mikrosystemtechnik Presynaptic cell Postsynaptic cell Neural vector Transgene transcription Ion channel Receptor Neurotransmitter precursor Transgene translation Ion channel Docking protein Re-uptake protein Second messenger