Mesoscale infraslow spontaneous membrane potential fluctuations recapitulate high-frequency activity cortical motifs

Neuroimaging of spontaneous, resting-state infraslow (<0.1 Hz) brain activity has been used to reveal the regional functional organization of the brain and may lead to the identification of novel biomarkers of neurological disease. However, these imaging studies generally rely on indirect measures of neuronal activity and the nature of the neuronal activity correlate remains unclear. Here we show, using wide-field, voltage-sensitive dye imaging, the mesoscale spatiotemporal structure and pharmacological dependence of spontaneous, infraslow cortical activity in anaesthetized and awake mice. Spontaneous infraslow activity is regionally distinct, correlates with electroencephalography and local field potential recordings, and shows bilateral symmetry between cortical hemispheres. Infraslow activity is attenuated and its functional structure abolished after treatment with voltage-gated sodium channel and glutamate receptor antagonists. Correlation analysis reveals patterns of infraslow regional connectivity that are analogous to cortical motifs observed from higher-frequency spontaneous activity and reflect the underlying framework of intracortical axonal projections.

[1]  David Kleinfeld,et al.  Chronic optical access through a polished and reinforced thinned skull. , 2010, Nature methods.

[2]  Abraham Z. Snyder,et al.  Imaging of Functional Connectivity in the Mouse Brain , 2011, PloS one.

[3]  Justin L. Vincent,et al.  Intrinsic functional architecture in the anaesthetized monkey brain , 2007, Nature.

[4]  T. Murphy,et al.  In vivo Large-Scale Cortical Mapping Using Channelrhodopsin-2 Stimulation in Transgenic Mice Reveals Asymmetric and Reciprocal Relationships between Cortical Areas , 2012, Front. Neural Circuits.

[5]  Walther Akemann,et al.  Imaging neural circuit dynamics with a voltage-sensitive fluorescent protein. , 2012, Journal of neurophysiology.

[6]  Marat Minlebaev,et al.  A Conserved Switch in Sensory Processing Prepares Developing Neocortex for Vision , 2010, Neuron.

[7]  M. Corbetta,et al.  Temporal dynamics of spontaneous MEG activity in brain networks , 2010, Proceedings of the National Academy of Sciences.

[8]  D. Kleinfeld,et al.  Stimulus-Induced Changes in Blood Flow and 2-Deoxyglucose Uptake Dissociate in Ipsilateral Somatosensory Cortex , 2008, The Journal of Neuroscience.

[9]  Justin L. Vincent,et al.  Intrinsic Fluctuations within Cortical Systems Account for Intertrial Variability in Human Behavior , 2007, Neuron.

[10]  M. Raichle,et al.  Cortical network functional connectivity in the descent to sleep , 2009, Proceedings of the National Academy of Sciences.

[11]  D. Leopold,et al.  Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: Implications for functional connectivity at rest , 2008, Human brain mapping.

[12]  M. Lauritzen,et al.  Coupling and uncoupling of activity‐dependent increases of neuronal activity and blood flow in rat somatosensory cortex , 2001, The Journal of physiology.

[13]  M. Raichle,et al.  Disease and the brain's dark energy , 2010, Nature Reviews Neurology.

[14]  Maurizio Corbetta,et al.  Functional connectivity and neurological recovery. , 2012, Developmental psychobiology.

[15]  D. McVea,et al.  Mirrored Bilateral Slow-Wave Cortical Activity within Local Circuits Revealed by Fast Bihemispheric Voltage-Sensitive Dye Imaging in Anesthetized and Awake Mice , 2010, The Journal of Neuroscience.

[16]  Waqas Majeed,et al.  Spatiotemporal dynamics of low frequency fluctuations in BOLD fMRI of the rat , 2009, Journal of magnetic resonance imaging : JMRI.

[17]  Rustem Khazipov,et al.  Spontaneous activity in developing sensory circuits: Implications for resting state fMRI , 2012, NeuroImage.

[18]  Biyu J. He,et al.  The Temporal Structures and Functional Significance of Scale-free Brain Activity , 2010, Neuron.

[19]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[20]  I. Fried,et al.  Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex , 2008, Nature Neuroscience.

[21]  M. Fox,et al.  The global signal and observed anticorrelated resting state brain networks. , 2009, Journal of neurophysiology.

[22]  J. Palva,et al.  Very Slow EEG Fluctuations Predict the Dynamics of Stimulus Detection and Oscillation Amplitudes in Humans , 2008, The Journal of Neuroscience.

[23]  J. Palva,et al.  Infraslow oscillations modulate excitability and interictal epileptic activity in the human cortex during sleep. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[24]  D. McVea,et al.  Spontaneous cortical activity alternates between motifs defined by regional axonal projections , 2013, Nature Neuroscience.

[25]  M. Steriade,et al.  A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  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.

[27]  G. Buzsáki,et al.  Neuronal Oscillations in Cortical Networks , 2004, Science.

[28]  T. Wiesel,et al.  Functional architecture of cortex revealed by optical imaging of intrinsic signals , 1986, Nature.

[29]  A. Grinvald,et al.  Imaging Cortical Dynamics at High Spatial and Temporal Resolution with Novel Blue Voltage-Sensitive Dyes , 1999, Neuron.

[30]  M. Schölvinck,et al.  Neural basis of global resting-state fMRI activity , 2010, Proceedings of the National Academy of Sciences.

[31]  Peter A. Bandettini,et al.  Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI , 2006, NeuroImage.

[32]  A. Grinvald,et al.  Spatiotemporal Dynamics of Sensory Responses in Layer 2/3 of Rat Barrel Cortex Measured In Vivo by Voltage-Sensitive Dye Imaging Combined with Whole-Cell Voltage Recordings and Neuron Reconstructions , 2003, The Journal of Neuroscience.

[33]  Justin L. Vincent,et al.  Disruption of Large-Scale Brain Systems in Advanced Aging , 2007, Neuron.

[34]  A. Braun,et al.  Decoupling of the brain's default mode network during deep sleep , 2009, Proceedings of the National Academy of Sciences.

[35]  Thomas K. Berger,et al.  Combined voltage and calcium epifluorescence imaging in vitro and in vivo reveals subthreshold and suprathreshold dynamics of mouse barrel cortex. , 2007, Journal of neurophysiology.

[36]  Amiram Grinvald,et al.  VSDI: a new era in functional imaging of cortical dynamics , 2004, Nature Reviews Neuroscience.

[37]  A. Grinvald,et al.  Spontaneously emerging cortical representations of visual attributes , 2003, Nature.

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

[39]  M Steriade,et al.  Intracellular analysis of relations between the slow (< 1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[40]  Biyu J. He,et al.  The fMRI signal, slow cortical potential and consciousness , 2009, Trends in Cognitive Sciences.

[41]  N. A. ALADJALOVA,et al.  Infra-Slow Rhythmic Oscillations of The Steady Potential of the Cerebral Cortex , 1957, Nature.

[42]  F. Haiss,et al.  Spatiotemporal Dynamics of Cortical Sensorimotor Integration in Behaving Mice , 2007, Neuron.

[43]  D. Kleinfeld,et al.  Finding coherence in spontaneous oscillations , 2008, Nature Neuroscience.

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

[45]  Biyu J. He,et al.  Electrophysiological correlates of the brain's intrinsic large-scale functional architecture , 2008, Proceedings of the National Academy of Sciences.

[46]  D. Kleinfeld,et al.  Visual stimuli induce waves of electrical activity in turtle cortex. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Kevin Murphy,et al.  The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? , 2009, NeuroImage.

[48]  Dieter Jaeger,et al.  Infraslow LFP correlates to resting-state fMRI BOLD signals , 2013, NeuroImage.

[49]  Abraham Z. Snyder,et al.  Optical imaging of disrupted functional connectivity following ischemic stroke in mice , 2014, NeuroImage.

[50]  M. Raichle,et al.  Rat brains also have a default mode network , 2012, Proceedings of the National Academy of Sciences.

[51]  M. Raichle,et al.  Resting State Functional Connectivity in Preclinical Alzheimer’s Disease , 2013, Biological Psychiatry.

[52]  Timothy H. Murphy,et al.  Distinct Cortical Circuit Mechanisms for Complex Forelimb Movement and Motor Map Topography , 2012, Neuron.

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

[54]  N. Logothetis,et al.  Neurophysiology of the BOLD fMRI Signal in Awake Monkeys , 2008, Current Biology.

[55]  Thomas Knöpfel,et al.  Genetically encoded optical indicators for the analysis of neuronal circuits , 2012, Nature Reviews Neuroscience.

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

[57]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[58]  Katsuei Shibuki,et al.  Dynamic Imaging of Somatosensory Cortical activity in the Rat Visualized by Flavoprotein Autofluorescence , 2003, The Journal of physiology.

[59]  T. Murphy,et al.  Prolonged Deficits in Parvalbumin Neuron Stimulation-Evoked Network Activity Despite Recovery of Dendritic Structure and Excitability in the Somatosensory Cortex following Global Ischemia in Mice , 2014, The Journal of Neuroscience.

[60]  N. Matsuki,et al.  Large-Scale Calcium Waves Traveling through Astrocytic Networks In Vivo , 2011, The Journal of Neuroscience.

[61]  M. Fukunaga,et al.  Low frequency BOLD fluctuations during resting wakefulness and light sleep: A simultaneous EEG‐fMRI study , 2008, Human brain mapping.

[62]  Timothy H. Murphy,et al.  Improved methods for chronic light-based motor mapping in mice: automated movement tracking with accelerometers, and chronic EEG recording in a bilateral thin-skull preparation , 2013, Front. Neural Circuits.

[63]  Nick C Fox,et al.  Regional variability of imaging biomarkers in autosomal dominant Alzheimer’s disease , 2013, Proceedings of the National Academy of Sciences.

[64]  Elizabeth A. Clement,et al.  Cyclic and Sleep-Like Spontaneous Alternations of Brain State Under Urethane Anaesthesia , 2008, PloS one.

[65]  Majid H. Mohajerani,et al.  Targeted mini-strokes produce changes in interhemispheric sensory signal processing that are indicative of disinhibition within minutes , 2011, Proceedings of the National Academy of Sciences.

[66]  P. Drew,et al.  Neurovascular Coupling and Decoupling in the Cortex during Voluntary Locomotion , 2014, The Journal of Neuroscience.

[67]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[68]  Abraham Z. Snyder,et al.  A default mode of brain function: A brief history of an evolving idea , 2007, NeuroImage.