Stimulus-Induced Changes in Blood Flow and 2-Deoxyglucose Uptake Dissociate in Ipsilateral Somatosensory Cortex

The present study addresses the relationship between blood flow and glucose consumption in rat primary somatosensory cortex (SI) in vivo. We examined bilateral neuronal and hemodynamic changes and 2-deoxyglucose (2DG) uptake, as measured by autoradiography, in response to unilateral forepaw stimulation. In contrast to the contralateral forepaw area, where neuronal activity, blood oxygenation/flow and 2DG uptake increased in unison, we observed, in the ipsilateral SI, a blood oxygenation/flow decrease and arteriolar vasoconstriction in the presence of increased 2DG uptake. Laminar electrophysiological recordings revealed an increase in ipsilateral spiking consistent with the observed increase in 2DG uptake. The vasoconstriction and the decrease in blood flow in the presence of an increase in 2DG uptake in the ipsilateral SI contradict the prominent metabolic hypothesis regarding the regulation of cerebral blood flow, which postulates that the state of neuroglial energy consumption determines the regional blood flow through the production of vasoactive metabolites. We propose that other factors, such as neuronal (and glial) release of messenger molecules, might play a dominant role in the regulation of blood flow in vivo in response to a physiological stimulus.

[1]  Grant R. Gordon,et al.  Brain metabolism dictates the polarity of astrocyte control over arterioles , 2008, Nature.

[2]  H. Berg,et al.  Supporting Online Material Materials and Methods Som Text Figs. S1 to S7 Tables S1 to S3 References Movies S1 to S6 Tuned Responses of Astrocytes and Their Influence on Hemodynamic Signals in the Visual Cortex , 2022 .

[3]  N. Logothetis.  What we can do and what we cannot do with fMRI , 2008, Nature.

[4]  A. Lowe,et al.  Sensory inputs from whisking movements modify cortical whisker maps visualized with functional magnetic resonance imaging. , 2008, Cerebral cortex.

[5]  J. Filosa,et al.  Tone-dependent vascular responses to astrocyte-derived signals. , 2008, American journal of physiology. Heart and circulatory physiology.

[6]  C. Iadecola,et al.  Glial regulation of the cerebral microvasculature , 2007, Nature Neuroscience.

[7]  Nikos K Logothetis,et al.  The ins and outs of fMRI signals , 2007, Nature Neuroscience.

[8]  D. Bressler,et al.  Negative BOLD fMRI Response in the Visual Cortex Carries Precise Stimulus-Specific Information , 2007, PloS one.

[9]  K. Svoboda,et al.  Channelrhodopsin-2–assisted circuit mapping of long-range callosal projections , 2007, Nature Neuroscience.

[10]  D. Kleinfeld,et al.  Suppressed Neuronal Activity and Concurrent Arteriolar Vasoconstriction May Explain Negative Blood Oxygenation Level-Dependent Signal , 2007, The Journal of Neuroscience.

[11]  D. Kleinfeld,et al.  Is there a common origin to surround-inhibition as seen through electrical activity versus hemodynamic changes? Focus on "Duration-dependent response in SI to vibrotactile stimulation in squirrel monkey". , 2007, Journal of neurophysiology.

[12]  Quanxin Wang,et al.  In vivo transcranial imaging of connections in mouse visual cortex , 2007, Journal of Neuroscience Methods.

[13]  Naoshige Uchida,et al.  Sensory-Evoked Intrinsic Optical Signals in the Olfactory Bulb Are Coupled to Glutamate Release and Uptake , 2006, Neuron.

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

[15]  G. Carmignoto,et al.  Astrocyte control of synaptic transmission and neurovascular coupling. , 2006, Physiological reviews.

[16]  J. Rossier,et al.  Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum , 2006, The Journal of Neuroscience.

[17]  P. Magistretti.  Neuron–glia metabolic coupling and plasticity , 2006, Journal of Experimental Biology.

[18]  Riitta Hari,et al.  Transient Suppression of Ipsilateral Primary Somatosensory Cortex during Tactile Finger Stimulation , 2006, The Journal of Neuroscience.

[19]  N. Logothetis,et al.  Negative functional MRI response correlates with decreases in neuronal activity in monkey visual area V1 , 2006, Nature Neuroscience.

[20]  Eric A Newman,et al.  Glial Cells Dilate and Constrict Blood Vessels: A Mechanism of Neurovascular Coupling , 2006, The Journal of Neuroscience.

[21]  E. Hamel.  Perivascular nerves and the regulation of cerebrovascular tone. , 2006, Journal of applied physiology.

[22]  T. Takano,et al.  Astrocyte-mediated control of cerebral blood flow , 2006, Nature Neuroscience.

[23]  D. Kleinfeld,et al.  Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke , 2006, Nature Methods.

[24]  D. Kleinfeld,et al.  Two-Photon Imaging of Cortical Surface Microvessels Reveals a Robust Redistribution in Blood Flow after Vascular Occlusion , 2006, PLoS biology.

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

[26]  M. Lauritzen.  Reading vascular changes in brain imaging: is dendritic calcium the key? , 2005, Nature Reviews Neuroscience.

[27]  A. Grinvald,et al.  Optical imaging of architecture and function in the living brain sheds new light on cortical mechanisms underlying visual perception , 2005, Brain Topography.

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

[29]  B. MacVicar,et al.  Calcium transients in astrocyte endfeet cause cerebrovascular constrictions , 2004, Nature.

[30]  Fahmeed Hyder,et al.  Energetic basis of brain activity: implications for neuroimaging , 2004, Trends in Neurosciences.

[31]  C. Iadecola.  Neurovascular regulation in the normal brain and in Alzheimer's disease , 2004, Nature Reviews Neuroscience.

[32]  Andrei G. Vlassenko,et al.  Increased lactate/pyruvate ratio augments blood flow in physiologically activated human brain. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[33]  J. Williamson,et al.  NADH augments blood flow in physiologically activated retina and visual cortex. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[34]  N. Logothetis.  The Underpinnings of the BOLD Functional Magnetic Resonance Imaging Signal , 2003, The Journal of Neuroscience.

[35]  A. Grinvald,et al.  Imaging Spatiotemporal Dynamics of Surround Inhibition in the Barrels Somatosensory Cortex , 2003, The Journal of Neuroscience.

[36]  M. C. Angulo,et al.  Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation , 2003, Nature Neuroscience.

[37]  A. Dale,et al.  Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation. , 2003, Optics letters.

[38]  A. Shmuel,et al.  Sustained Negative BOLD, Blood Flow and Oxygen Consumption Response and Its Coupling to the Positive Response in the Human Brain , 2002, Neuron.

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

[40]  N. Logothetis.  The neural basis of the blood-oxygen-level-dependent functional magnetic resonance imaging signal. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[41]  Fahmeed Hyder,et al.  Biophysical basis of brain activity: implications for neuroimaging , 2002, Quarterly Reviews of Biophysics (print).

[42]  B. Weber,et al.  White Matter Glucose Metabolism during Intracortical Electrostimulation: A Quantitative [18F]Fluorodeoxyglucose Autoradiography Study in the Rat , 2002, NeuroImage.

[43]  J. Mayhew,et al.  Changes in Blood Flow, Oxygenation, and Volume Following Extended Stimulation of Rodent Barrel Cortex , 2002, NeuroImage.

[44]  J. Briers,et al.  Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging. , 2001, Physiological measurement.

[45]  S. Laughlin,et al.  An Energy Budget for Signaling in the Grey Matter of the Brain , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[46]  M A Nicolelis,et al.  Bilateral Integration of Whisker Information in the Primary Somatosensory Cortex of Rats , 2001, The Journal of Neuroscience.

[47]  L. Sokoloff,et al.  Effects of anesthesia on functional activation of cerebral blood flow and metabolism , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[48]  István Ulbert,et al.  Multiple microelectrode-recording system for human intracortical applications , 2001, Journal of Neuroscience Methods.

[49]  M. Moskowitz,et al.  Dynamic Imaging of Cerebral Blood Flow Using Laser Speckle , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[50]  J. Mayhew,et al.  Spectroscopic Analysis of Neural Activity in Brain: Increased Oxygen Consumption Following Activation of Barrel Cortex , 2000, NeuroImage.

[51]  A. Villringer,et al.  Physical model for the spectroscopic analysis of cortical intrinsic optical signals. , 2000, Physics in medicine and biology.

[52]  A. Grinvald,et al.  Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging. , 1999, Science.

[53]  P. Magistretti,et al.  Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[54]  C Sato,et al.  Analysis of Optical Signals Evoked by Peripheral Nerve Stimulation in Rat Somatosensory Cortex: Dynamic Changes in Hemoglobin Concentration and Oxygenation , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[55]  R G Shulman,et al.  Energy on Demand , 1999, Science.

[56]  D. Kleinfeld,et al.  Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[57]  A. Dale,et al.  The Retinotopy of Visual Spatial Attention , 1998, Neuron.

[58]  M Hallett,et al.  Inhibitory influence of the ipsilateral motor cortex on responses to stimulation of the human cortex and pyramidal tract , 1998, The Journal of physiology.

[59]  F. Ismail-Beigi,et al.  Glycemia-lowering effect of cobalt chloride in the diabetic rat: role of decreased gluconeogenesis. , 1998, American journal of physiology. Endocrinology and metabolism.

[60]  S Meiman,et al.  A detailed analysis of charges for hematopoietic stem cell transplantation at a children’s hospital , 1998, Bone Marrow Transplantation.

[61]  G. Bonvento,et al.  Local Uncoupling of the Cerebrovascular and Metabolic Responses to Somatosensory Stimulation after Neuronal Nitric Oxide Synthase Inhibition , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[62]  G. Bonvento,et al.  Autoradiographic Evidence for Flow-Metabolism Uncoupling During Stimulation of the Nucleus Basalis of Meynert in the Conscious Rat , 1997, Journal of Cerebral Blood Flow and Metabolism.

[63]  D. Kleinfeld,et al.  Distributed representation of vibrissa movement in the upper layers of somatosensory cortex revealed with voltage‐sensitive dyes , 1996, The Journal of comparative neurology.

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

[65]  A. Toga,et al.  Functional Increases in Cerebral Blood Volume over Somatosensory Cortex , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[66]  B. Meyer,et al.  Inhibitory and excitatory interhemispheric transfers between motor cortical areas in normal humans and patients with abnormalities of the corpus callosum. , 1995, Brain : a journal of neurology.

[67]  Arthur W. Toga,et al.  Imaging Optical Reflectance in Rodent Barrel and Forelimb Sensory Cortex , 1994, NeuroImage.

[68]  B. Day,et al.  Interhemispheric inhibition of the human motor cortex. , 1992, The Journal of physiology.

[69]  M. Ueki,et al.  Effect of alpha‐chloralose, halothane, pentobarbital and nitrous oxide anesthesia on metabolic coupling in somatosensory cortex of rat , 1992, Acta anaesthesiologica Scandinavica.

[70]  J. Olavarria,et al.  Areal and laminar organization of corticocortical projections in the rat somatosensory cortex , 1990, The Journal of comparative neurology.

[71]  D. Ts'o,et al.  Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[72]  M. Mintun,et al.  Nonoxidative glucose consumption during focal physiologic neural activity. , 1988, Science.

[73]  E. Switkes,et al.  Functional anatomy of macaque striate cortex. I. Ocular dominance, binocular interactions, and baseline conditions , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[74]  E. Switkes,et al.  Functional anatomy of macaque striate cortex. III. Color , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[75]  H. Killackey,et al.  Differential distribution of callosal projection neurons in the neonatal and adult rat , 1979, Brain Research.

[76]  E. White,et al.  Afferent and efferent projections of the region in mouse sml cortex which contains the posteromedial barrel subfield , 1977, The Journal of comparative neurology.

[77]  M. Reivich,et al.  THE [14C]DEOXYGLUCOSE METHOD FOR THE MEASUREMENT OF LOCAL CEREBRAL GLUCOSE UTILIZATION: THEORY, PROCEDURE, AND NORMAL VALUES IN THE CONSCIOUS AND ANESTHETIZED ALBINO RAT 1 , 1977, Journal of neurochemistry.

[78]  E. G. Jones,et al.  The organization and postnatal development of the commissural projection of the rat somatic sensory cortex , 1976, The Journal of comparative neurology.