Hemodynamic Responses Evoked by Neuronal Stimulation via Channelrhodopsin-2 Can Be Independent of Intracortical Glutamatergic Synaptic Transmission

Scott, Nadia Aleyna; Murphy, Timothy H.

doi:10.1371/journal.pone.0029859

Cited by 53 publications

(66 citation statements)

References 36 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…30 This issue could be addressed by studying specific cell types in conjunction with pharmacological synaptic blockers. 9 Optogenetics is a potentially useful method for studying neurovascular coupling, and understanding the metabolic effects of optogenetic stimulation is increasingly important as optogenetics is applied throughout neurophysiology research. Channelrhodopsin-2 stimulation creates large cationic currents, and maintaining ionic gradients is highly energy demanding.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6][7][8] Such a spatial approach in the cortex would build upon previous temporal approaches for studying the hemodynamic response with optogenetics. Laser speckle contrast imaging, [9][10][11] intrinsic optical signal imaging, 9,12,13 and functional magnetic resonance imaging (fMRI) [14][15][16] have been combined with temporal optogenetic modulation to investigate cerebral hemodynamics.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Patterned Optogenetic Modulation of Neurovascular and Metabolic Signals

Richner

Baumgartner

Brodnick

et al. 2014

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Patterned Optogenetic Modulation of Neurovascular and Metabolic Signals

Richner

Baumgartner

Brodnick

et al. 2014

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…Relatedly, an earlier study with transgenic mice expressing ChR2 in layer V reported that an ionotropic GluR antagonist did not reduce dHb-weighted OIS and CBF responses evoked by photo-stimulation. The transgenic mice in this study 10 have expression of ChR2 only in a deeper layer (V) and the antagonists may not fully reach these layers.…”

Section: Glutamate Receptor Blockmentioning

confidence: 94%

“…Unlike sensory stimulation, the hemodynamic response to optogenetic stimulation was shown to correlate better with the neuronal firing rate than the local field potential (LFP), 9 and a blockade of ionotropic glutamate receptors (GluRs) did not change the hemodynamic response to optical stimulation of excitatory neurons. 10 These studies of ChR2 transgenic mice have not been reproduced in different species or expression systems, thus it is essential to reexamine the above-mentioned issues in ChR2 expressing rats for the adoption of mouse neurovascular research findings to opto-fMRI in rats.…”

Section: Introductionmentioning

confidence: 99%

Neural and Hemodynamic Responses to Optogenetic and Sensory Stimulation in the Rat Somatosensory Cortex

Iordanova

Vazquez

Poplawsky

et al. 2015

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Introducing optogenetics into neurovascular research can provide novel insights into the cell-specific control of the hemodynamic response. To generalize findings from molecular approaches, it is crucial to determine whether light-activated circuits have the same effect on the vasculature as sensory-activated ones. For that purpose, rats expressing channelrhodopsin (ChR2) specific to excitatory glutamatergic neurons were used to measure neural activity, blood flow, hemoglobin-based optical intrinsic signal, and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) during optogenetic and sensory stimulation. The magnitude of the evoked hemodynamic responses was monotonically correlated with optogenetic stimulus strength. The BOLD hemodynamic response function was consistent for optogenetic and sensory stimuli. The relationship between electrical activities and hemodynamic responses was comparable for optogenetic and sensory stimuli, and better explained by the local field potential (LFP) than the firing rate. The LFP was well correlated with cerebral blood flow, moderately with cerebral blood volume, and less with deoxyhemoglobin (dHb) level. The presynaptic firing rate had little impact on evoking vascular response. Contribution of the postsynaptic LFP to the blood flow response induced by optogenetic stimulus was further confirmed by the application of glutamate receptor antagonists. Overall, neurovascular coupling during optogenetic control of glutamatergic neurons largely conforms to that of a sensory stimulus.

show abstract

“…Although this system made it easy to apply optogenetics to free-moving animals, it is still invasive-wireless headstagemounted systems still need to implant optical fiber into the brain. To reduce invasiveness channels that respond to longer wavelength light have been developed; longer wavelength light penetrates tissue more deeply than short [135][136][137][138][139][140]. Red light-activated opsins such as excitatory red lightactivated channelrhodopsin and inhibitory red-shifted cruxhalorhodopsin (Jaws) can be applied to the surface of the brain or through a thinned skull [119,120].…”

Section: Optogeneticsmentioning

confidence: 99%

Selective Manipulation of Neural Circuits

Park

Carmel

2016

Neurotherapeutics

View full text Add to dashboard Cite

Unraveling the complex network of neural circuits that form the nervous system demands tools that can manipulate specific circuits. The recent evolution of genetic tools to target neural circuits allows an unprecedented precision in elucidating their function. Here we describe two general approaches for achieving circuit specificity. The first uses the genetic identity of a cell, such as a transcription factor unique to a circuit, to drive expression of a molecule that can manipulate cell function. The second uses the spatial connectivity of a circuit to achieve specificity: one genetic element is introduced at the origin of a circuit and the other at its termination. When the two genetic elements combine within a neuron, they can alter its function. These two general approaches can be combined to allow manipulation of neurons with a specific genetic identity by introducing a regulatory gene into the origin or termination of the circuit. We consider the advantages and disadvantages of both these general approaches with regard to specificity and efficacy of the manipulations. We also review the genetic techniques that allow gain-and loss-of-function within specific neural circuits. These approaches introduce light-sensitive channels (optogenetic) or drug sensitive channels (chemogenetic) into neurons that form specific circuits. We compare these tools with others developed for circuit-specific manipulation and describe the advantages of each. Finally, we discuss how these tools might be applied for identification of the neural circuits that mediate behavior and for repair of neural connections.

show abstract

Hemodynamic Responses Evoked by Neuronal Stimulation via Channelrhodopsin-2 Can Be Independent of Intracortical Glutamatergic Synaptic Transmission

Cited by 53 publications

References 36 publications

Patterned Optogenetic Modulation of Neurovascular and Metabolic Signals

Patterned Optogenetic Modulation of Neurovascular and Metabolic Signals

Neural and Hemodynamic Responses to Optogenetic and Sensory Stimulation in the Rat Somatosensory Cortex

Selective Manipulation of Neural Circuits

Contact Info

Product

Resources

About