Cortical Neurovascular Coupling Driven by Stimulation of Channelrhodopsin-2

While functional imaging is widely used in studies of the brain, how well the hemodynamic signal represents the underlying neural activity is still unclear. And there is a debate on whether hemodynamic signal is more tightly related to synaptic activity or action potentials. This study intends to address these questions by examining neurovascular coupling driven by pyramidal cells in the motor cortex of rats. Pyramidal cells in the motor cortex of rats were selectively transduced with the light sensitive cation channel channelrhodopsin-2 (ChR2). Electrophysiological recordings and optical intrinsic signal imaging were performed simultaneously and synchronously to capture the neural activity and hemodynamics induced by optical stimulation of ChR2-expressing pyramidal cells. Our results indicate that both synaptic activity (local field potential, LFP) and action potentials (multi-unit activity, MUA) are tightly related to hemodynamic signals. While LFPs in γ band are better in predicting hemodynamic signals elicited by short stimuli, MUA has better predictions to hemodynamic signals elicited by long stimuli. Our results also indicate that strong nonlinearity exists in neurovascular coupling.

[1]  W. Singer,et al.  Hemodynamic Signals Correlate Tightly with Synchronized Gamma Oscillations , 2005, Science.

[2]  Feng Zhang,et al.  Channelrhodopsin-2 and optical control of excitable cells , 2006, Nature Methods.

[3]  A. Toga,et al.  Linear and Nonlinear Relationships between Neuronal Activity, Oxygen Metabolism, and Hemodynamic Responses , 2004, Neuron.

[4]  F. Hyder,et al.  Cerebral energetics and spiking frequency: The neurophysiological basis of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Yevgeniy B. Sirotin,et al.  Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity. , 2009, Nature.

[6]  Dae-Shik Kim,et al.  Global and local fMRI signals driven by neurons defined optogenetically by type and wiring , 2010, Nature.

[7]  D. Heeger,et al.  In this issue , 2002, Nature Reviews Drug Discovery.

[8]  D. Attwell,et al.  The neural basis of functional brain imaging signals , 2002, Trends in Neurosciences.

[9]  R. Freeman,et al.  Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity , 2007, Nature Neuroscience.

[10]  T. Murphy,et al.  Imaging the Impact of Cortical Microcirculation on Synaptic Structure and Sensory-Evoked Hemodynamic Responses In Vivo , 2007, PLoS biology.

[11]  Daniel Yoshor,et al.  Spatial Attention Does Not Strongly Modulate Neuronal Responses in Early Human Visual Cortex , 2007, The Journal of Neuroscience.

[12]  D. G. Albrecht,et al.  Spikes versus BOLD: what does neuroimaging tell us about neuronal activity? , 2000, Nature Neuroscience.

[13]  D. Heeger,et al.  Linear Systems Analysis of Functional Magnetic Resonance Imaging in Human V1 , 1996, The Journal of Neuroscience.

[14]  Seong-Gi Kim,et al.  Early Temporal Characteristics of Cerebral Blood Flow and Deoxyhemoglobin Changes during Somatosensory Stimulation , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  Anders M. Dale,et al.  Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex , 2005, NeuroImage.

[16]  A. Dale,et al.  Coupling of Total Hemoglobin Concentration, Oxygenation, and Neural Activity in Rat Somatosensory Cortex , 2003, Neuron.

[17]  D. Noll,et al.  Nonlinear Aspects of the BOLD Response in Functional MRI , 1998, NeuroImage.

[18]  S. Arridge,et al.  Estimation of optical pathlength through tissue from direct time of flight measurement , 1988 .

[19]  B. Rosen,et al.  Investigation of the early response to rat forepaw stimulation , 1999, Magnetic resonance in medicine.

[20]  Baowang Li,et al.  High-Resolution Neurometabolic Coupling in the Lateral Geniculate Nucleus , 2007, The Journal of Neuroscience.

[21]  G. Taga,et al.  Brain imaging in awake infants by near-infrared optical topography , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[22]  R. Freeman,et al.  Single-Neuron Activity and Tissue Oxygenation in the Cerebral Cortex , 2003, Science.

[23]  Kyung K Peck,et al.  Comparison of hemodynamic response nonlinearity across primary cortical areas , 2004, NeuroImage.

[24]  M. Mintun,et al.  Brain work and brain imaging. , 2006, Annual review of neuroscience.

[25]  R. Freeman,et al.  High-resolution neurometabolic coupling revealed by focal activation of visual neurons , 2004, Nature Neuroscience.

[26]  Ying Zheng,et al.  Long Duration Stimuli and Nonlinearities in the Neural–Haemodynamic Coupling , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[27]  J. Rossier,et al.  Cortical GABA Interneurons in Neurovascular Coupling: Relays for Subcortical Vasoactive Pathways , 2004, The Journal of Neuroscience.

[28]  L. Swanson The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[29]  A. Ngai,et al.  Frequency-dependent changes in cerebral blood flow and evoked potentials during somatosensory stimulation in the rat , 1999, Brain Research.

[30]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[31]  Dae-Shik Kim,et al.  High-resolution mapping of iso-orientation columns by fMRI , 2000, Nature Neuroscience.

[32]  A Villringer,et al.  Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide. , 1994, The American journal of physiology.

[33]  S. Ogawa,et al.  Oxygenation‐sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields , 1990, Magnetic resonance in medicine.

[34]  Jessica A. Cardin,et al.  Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2 , 2010, Nature Protocols.

[35]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[36]  Karl J. Friston,et al.  A direct quantitative relationship between the functional properties of human and macaque V5 , 2000, Nature Neuroscience.

[37]  Timothy H. Murphy,et al.  Hemodynamic Responses Evoked by Neuronal Stimulation via Channelrhodopsin-2 Can Be Independent of Intracortical Glutamatergic Synaptic Transmission , 2012, PloS one.

[38]  A. Grinvald,et al.  Interactions Between Electrical Activity and Cortical Microcirculation Revealed by Imaging Spectroscopy: Implications for Functional Brain Mapping , 1996, Science.

[39]  Josef Pfeuffer,et al.  Spatial dependence of the nonlinear BOLD response at short stimulus duration , 2002, NeuroImage.

[40]  Itamar Kahn,et al.  Characterization of the Functional MRI Response Temporal Linearity via Optical Control of Neocortical Pyramidal Neurons , 2011, The Journal of Neuroscience.