Patterned optogenetic modulation of neurovascular and metabolic signals.
The hemodynamic and metabolic response of the cortex depends spatially and temporally on the activity of multiple cell types. Optogenetics enables specific cell types to be modulated with high temporal precision and is therefore an emerging method for studying neurovascular and neurometabolic coupling. Going beyond temporal investigations, we developed a microprojection system to apply spatial photostimulus patterns in vivo. We monitored vascular and metabolic fluorescence signals after photostimulation in Thy1-channelrhodopsin-2 mice. Cerebral arteries increased in diameter rapidly after photostimulation, while nearby veins showed a slower smaller response. The amplitude of the arterial response was depended on the area of cortex stimulated. The fluorescence signal emitted at 450/100 nm and excited with ultraviolet is indicative of reduced nicotinamide adenine dinucleotide, an endogenous fluorescent enzyme involved in glycolysis and the citric acid cycle. This fluorescence signal decreased quickly and transiently after optogenetic stimulation, suggesting that glucose metabolism is tightly locked to optogenetic stimulation. To verify optogenetic stimulation of the cortex, we used a transparent substrate microelectrode array to map cortical potentials resulting from optogenetic stimulation. Spatial optogenetic stimulation is a new tool for studying neurovascular and neurometabolic coupling.
Laboratory for Optical and Computational Instrumentation and Department of Biomedical Engineering, University of Wisconsin at Madison, Madison, Wisconsin, USA.
Thomas J
TJ
Richner
Department of Electrical Engineering and Computer Science, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Ryan
R
Baumgartner
Laboratory for Optical and Computational Instrumentation and Department of Biomedical Engineering, University of Wisconsin at Madison, Madison, Wisconsin, USA.
Sarah K
SK
Brodnick
Department of Electrical Engineering and Computer Science, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Mehdi
M
Azimipour
Laboratory for Optical and Computational Instrumentation and Department of Biomedical Engineering, University of Wisconsin at Madison, Madison, Wisconsin, USA.
Lisa A
LA
Krugner-Higby
Laboratory for Optical and Computational Instrumentation and Department of Biomedical Engineering, University of Wisconsin at Madison, Madison, Wisconsin, USA.
Kevin W
KW
Eliceiri
Laboratory for Optical and Computational Instrumentation and Department of Biomedical Engineering, University of Wisconsin at Madison, Madison, Wisconsin, USA.
Justin C
JC
Williams
Department of Electrical Engineering and Computer Science, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
Ramin
R
Pashaie
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D002536:Cerebral Arteries / Q000294:innervation / Q000502:physiology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology*; D002550:Cerebral Veins / Q000294:innervation / Q000502:physiology*; D000075402:Channelrhodopsins; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004867:Equipment Design; D005071:Evoked Potentials / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics; D008822:Mice, Transgenic; D062308:Optogenetics / Q000295:instrumentation / Q000379:methods*; D010775:Photic Stimulation; D018800:Thy-1 Antigens / Q000235:genetics
D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D008164:Luminescent Proteins; D018800:Thy-1 Antigens; C054562:yellow fluorescent protein, Bacteria