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Spontaneous cortical activity alternates between motifs defined by regional axonal projections

Nature Neuroscience volume 16, pages 1426–1435 (2013)Cite this article

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Abstract

Using millisecond-timescale voltage-sensitive dye imaging in lightly anesthetized or awake adult mice, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing, including vision, audition and touch. We found similar cortical networks with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality-specific sources, such as primary sensory areas, a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area and a secondary anterior medial sink within the cingulate and secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range monosynaptic connections between cortical regions. Maps of intracortical monosynaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity.

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Figure 1: Unique and consensus activation patterns during multiple forms of sensory stimulation.
Figure 2: Sensory- and photostimulation-induced activation show modality-specific source locations and termination at a common sink location.
Figure 3: Spontaneous, sensory- and photostimulation-evoked cortical VSD maps share similar regional patterns.
Figure 4: Patterns of sensory-evoked and spontaneous activity in quiet awake mice are similar to those observed under anesthesia.
Figure 5: The correlation maps generated from sensory-evoked or spontaneous activity during quiet wakefulness are similar to the maps obtained during anesthesia.
Figure 6: Spontaneous cortical activity can be decomposed into unique repeating sensory motifs.
Figure 7: Comparison of cortical axonal projection patterns to correlation maps of spontaneous cortical activity.
Figure 8: Axonal projection maps are most similar to their corresponding functional maps.

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References

  1. Zhang, D. & Raichle, M.E. Disease and the brain's dark energy. Nat. Rev. Neurol. 6, 15–28 (2010).

    Article  PubMed  Google Scholar 

  2. Destexhe, A. & Contreras, D. Neuronal computations with stochastic network states. Science 314, 85–90 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Harris, K.D. & Thiele, A. Cortical state and attention. Nat. Rev. Neurosci. 12, 509–523 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Arieli, A., Sterkin, A., Grinvald, A. & Aertsen, A. Dynamics of ongoing activity: explanation of the large variability in evoked cortical responses. Science 273, 1868–1871 (1996).

    Article  CAS  PubMed  Google Scholar 

  5. Kenet, T., Bibitchkov, D., Tsodyks, M., Grinvald, A. & Arieli, A. Spontaneously emerging cortical representations of visual attributes. Nature 425, 954–956 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Ferezou, I. et al. Spatiotemporal dynamics of cortical sensorimotor integration in behaving mice. Neuron 56, 907–923 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Waters, J. & Helmchen, F. Background synaptic activity is sparse in neocortex. J. Neurosci. 26, 8267–8277 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Luczak, A., Bartho, P. & Harris, K.D. Spontaneous events outline the realm of possible sensory responses in neocortical populations. Neuron 62, 413–425 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Han, F., Caporale, N. & Dan, Y. Reverberation of recent visual experience in spontaneous cortical waves. Neuron 60, 321–327 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Vincent, J.L. et al. Intrinsic functional architecture in the anaesthetized monkey brain. Nature 447, 83–86 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Leopold, D.A., Murayama, Y. & Logothetis, N.K. Very slow activity fluctuations in monkey visual cortex: implications for functional brain imaging. Cereb. Cortex 13, 422–433 (2003).

    Article  PubMed  Google Scholar 

  12. Lu, H. et al. Rat brains also have a default mode network. Proc. Natl. Acad. Sci. USA 109, 3979–3984 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. de Pasquale, F. et al. A cortical core for dynamic integration of functional networks in the resting human brain. Neuron 74, 753–764 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hipp, J.F., Hawellek, D.J., Corbetta, M., Siegel, M. & Engel, A.K. Large-scale cortical correlation structure of spontaneous oscillatory activity. Nat. Neurosci. 15, 884–890 (2012).

    Article  CAS  PubMed  Google Scholar 

  15. Wedeen, V.J. et al. Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers. Neuroimage 41, 1267–1277 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Frostig, R.D., Xiong, Y., Chen-Bee, C.H., Kvasnak, E. & Stehberg, J. Large-scale organization of rat sensorimotor cortex based on a motif of large activation spreads. J. Neurosci. 28, 13274–13284 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. White, B.R. et al. Imaging of functional connectivity in the mouse brain. PLoS ONE 6, e16322 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Grinvald, A. & Hildesheim, R. VSDI: a new era in functional imaging of cortical dynamics. Nat. Rev. Neurosci. 5, 874–885 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Mohajerani, M.H., McVea, D.A., Fingas, M. & Murphy, T.H. Mirrored bilateral slow-wave cortical activity within local circuits revealed by fast bihemispheric voltage-sensitive dye imaging in anesthetized and awake mice. J. Neurosci. 30, 3745–3751 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Allen Institute for Brain Science. Allen Mouse Brain Connectivity Atlas. Allen Brain Atlas Data Portal 〈http://connectivity.brain-map.org/〉 (2012).

  21. Kleinfeld, D. & Delaney, K.R. Distributed representation of vibrissa movement in the upper layers of somatosensory cortex revealed with voltage-sensitive dyes. J. Comp. Neurol. 375, 89–108 (1996).

    Article  CAS  PubMed  Google Scholar 

  22. Lim, D.H. et al. In vivo large-scale cortical mapping using channelrhodopsin-2 stimulation in transgenic mice reveals asymmetric and reciprocal relationships between cortical areas. Front. Neural Circuits 6, 11 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Mao, T. et al. Long-range neuronal circuits underlying the interaction between sensory and motor cortex. Neuron 72, 111–123 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Grandy, T.H., Greenfield, S.A. & Devonshire, I.M. An evaluation of in vivo voltage-sensitive dyes: pharmacological side effects and signal-to-noise ratios after effective removal of brain-pulsation artifacts. J. Neurophysiol. 108, 2931–2945 (2012).

    Article  CAS  PubMed  Google Scholar 

  25. Akemann, W. et al. Imaging neural circuit dynamics with a voltage-sensitive fluorescent protein. J. Neurophysiol. 108, 2323–2337 (2012).

    Article  CAS  PubMed  Google Scholar 

  26. Liu, C. Beyond Pixels: Exploring New Representations and Applications for Motion Analysis. PhD thesis, Massachusetts Institute of Technology (2009).

  27. Takagaki, K., Zhang, C., Wu, J.Y. & Ohl, F.W. Flow detection of propagating waves with temporospatial correlation of activity. J. Neurosci. Methods 200, 207–218 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bullmore, E. & Sporns, O. Complex brain networks: graph theoretical analysis of structural and functional systems. Nat. Rev. Neurosci. 10, 186–198 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. Poulet, J.F. & Petersen, C.C. Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice. Nature 454, 881–885 (2008).

    Article  CAS  PubMed  Google Scholar 

  30. Haider, B., Hausser, M. & Carandini, M. Inhibition dominates sensory responses in the awake cortex. Nature 493, 97–100 (2013).

    Article  PubMed  Google Scholar 

  31. Polack, P.O. & Contreras, D. Long-range parallel processing and local recurrent activity in the visual cortex of the mouse. J. Neurosci. 32, 11120–11131 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Huang, X. et al. Spiral wave dynamics in neocortex. Neuron 68, 978–990 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sato, T.K., Nauhaus, I. & Carandini, M. Traveling waves in visual cortex. Neuron 75, 218–229 (2012).

    Article  CAS  PubMed  Google Scholar 

  34. Niell, C.M. & Stryker, M.P. Modulation of visual responses by behavioral state in mouse visual cortex. Neuron 65, 472–479 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wilson, M.A. & McNaughton, B.L. Reactivation of hippocampal ensemble memories during sleep. Science 265, 676–679 (1994).

    CAS  PubMed  Google Scholar 

  36. Euston, D.R., Tatsuno, M. & McNaughton, B.L. Fast-forward playback of recent memory sequences in prefrontal cortex during sleep. Science 318, 1147–1150 (2007).

    Article  CAS  PubMed  Google Scholar 

  37. Douglas, R.J. & Martin, K.A. Mapping the matrix: the ways of neocortex. Neuron 56, 226–238 (2007).

    Article  CAS  PubMed  Google Scholar 

  38. Reid, R.C. From functional architecture to functional connectomics. Neuron 75, 209–217 (2012).

    Article  CAS  PubMed  Google Scholar 

  39. Shmuel, A. & Leopold, D.A. Neuronal correlates of spontaneous fluctuations in fMRI signals in monkey visual cortex: implications for functional connectivity at rest. Hum. Brain Mapp. 29, 751–761 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Grienberger, C. et al. Sound-evoked network calcium transients in mouse auditory cortex in vivo. J. Physiol. (Lond.) 590, 899–918 (2012).

    Article  CAS  Google Scholar 

  41. Buzsaki, G. et al. Nucleus basalis and thalamic control of neocortical activity in the freely moving rat. J. Neurosci. 8, 4007–4026 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Beier, K.T. et al. Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors. Proc. Natl. Acad. Sci. USA 108, 15414–15419 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Osakada, F. et al. New rabies virus variants for monitoring and manipulating activity and gene expression in defined neural circuits. Neuron 71, 617–631 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cardin, J.A. et al. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459, 663–667 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tamamaki, N. & Tomioka, R. Long-range GABAergic connections distributed throughout the neocortex and their possible function. Front. Neurosci. 4, 202 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Alivisatos, A.P. et al. The brain activity map project and the challenge of functional connectomics. Neuron 74, 970–974 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bohland, J.W. et al. A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale. PLoS Comput. Biol. 5, e1000334 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Li, A. et al. Micro-optical sectioning tomography to obtain a high-resolution atlas of the mouse brain. Science 330, 1404–1408 (2010).

    Article  CAS  PubMed  Google Scholar 

  49. Kleinfeld, D. et al. Large-scale automated histology in the pursuit of connectomes. J. Neurosci. 31, 16125–16138 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Azin, M., Guggenmos, D.J., Barbay, S., Nudo, R.J. & Mohseni, P. A miniaturized system for spike-triggered intracortical microstimulation in an ambulatory rat. IEEE Trans. Biomed. Eng. 58, 2589–2597 (2011).

    Article  PubMed  Google Scholar 

  51. Shoham, D. et al. Imaging cortical dynamics at high spatial and temporal resolution with novel blue voltage-sensitive dyes. Neuron 24, 791–802 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Paxinos, G. & Franklin, K.B.J. The Mouse Brain in Stereotaxic Coordinates (Elsevier Academic Press, Amsterdam, Boston, 2004).

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Acknowledgements

This work was supported by Canadian Institutes of Health Research (CIHR) Operating Grant MOP-12675 (T.H.M.), a Human Frontier Science Program grant (T.H.M.), Michael Smith Foundation for Health Research postdoctoral fellowships (M.H.M. and A.W.C.), a CIHR Operating Grant (Y.T.W.), Heart and Stroke Foundation of Canada postdoctoral fellowships (M.H.M. and A.W.C.) and a CIHR Focus on Stroke postdoctoral fellowship (M.H.M.). We thank the Allen Institute for Brain Science for providing a database of axonal projections. We thank P. Wang and C. Jiang for surgical assistance.

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Author notes

  1. Majid H Mohajerani

    Present address: Present address: Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada.,

  2. Majid H Mohajerani and Allen W Chan: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada

    Majid H Mohajerani, Allen W Chan, Mostafa Mohsenvand, Jeffrey LeDue, Rui Liu, David A McVea, Jamie D Boyd & Timothy H Murphy

  2. Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

    Majid H Mohajerani, Allen W Chan, Mostafa Mohsenvand, Jeffrey LeDue, David A McVea, Jamie D Boyd, Yu Tian Wang & Timothy H Murphy

  3. Department of Medicine and Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada

    Allen W Chan & Yu Tian Wang

  4. Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA

    Mark Reimers

  5. Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada

    Timothy H Murphy

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Contributions

M.H.M. and T.H.M. designed the study. M.H.M., A.W.C., D.A.M. and J.L. performed the experiments. M.H.M., A.W.C., M.M., J.L., Y.T.W. and M.R. analyzed the data. M.H.M., R.L., J.L. and J.D.B. participated in processing the Allen Mouse Brain Connectivity data. M.H.M., A.W.C. and T.H.M. wrote the manuscript, which all authors commented on and edited. T.H.M. supervised the study.

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Correspondence to Timothy H Murphy.

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Supplementary information

Supplementary Text and Figures

Supplementary Figures 1-10 (PDF 3997 kb)

Unique regional patterns of cortical depolarization after different forms of sensory stimulation.

Tone (1ms, 25 KHz), C2 whisker (1ms, tactile stimulation using piezo), visual (1ms, green and blue LED), forelimb (1ms, 1mA), and hindlimb (1ms, 1mA) evoked VSD response were imaged in an isoflurane anesthetized mouse. The imaging area included: primary (motor, somatosensory, visual, Auditory), secondary (motor, visual, somatosensory) and association (retrosplenial, cingulate) cortices. (AVI 2015 kb)

Spontaneous cortical activity in an anesthetized mouse.

Spontaneous cortical activity across the right hemisphere imaged in an isoflurane (0.5%) anesthetized mouse. The VSD signal of spontaneous cortical activity was filtered (0.1-6 Hz) using a zero-phase Chebyshev bandpass filter. (AVI 19426 kb)

Optical flow measurement of C2 whisker-evoked VSD response.

Whisker stimulation-evoked VSD activation (average of 20 trials). Left, black arrows indicate the direction of velocity of VSD signal spread. Relative magnitude of velocity is indicated by arrows size. Right, for response in left, measurements of absolute velocity are represented in pseudocolor. Streamlines indicate local direction of velocity flow. (AVI 2236 kb)

Time evolution of seed-pixel correlation map.

Spontaneous cortical activity in an isoflurane (0.5%) anesthetized mouse alongside the cumulative seed-pixel based correlation maps for the forelimb cortex. (AVI 12135 kb)

41593_2013_BFnn3499_MOESM17_ESM.avi

The spatiotemporal dynamics of visual-evoked VSD response under conditions of isoflurane anesthesia or in a quiet awake state. (AVI 629 kb)

Example of averaged hindlimb-evoked VSD response followed by an example of a hindlimb-evoked-like event within spontaneous activity.

The hindlimb evoked response is the average of 10 trials of contralateral (left) hindlimb stimulation. Episodes of spontaneous activity were detected by cross-correlation analysis of spontaneous activity and a 3-frame hindlimb response template that exceeded threshold criteria (see Methods). The detected hindlimb-evoked-like spontaneous events were then aligned by the start of the template and averaged to make the movie. (AVI 1616 kb)

Example of averaged whisker-evoked VSD response followed by an example of a whisker-evoked-like event within spontaneous activity.

The whisker evoked response is the average of 10 trials of contralateral (left) whisker stimulation. Episodes of spontaneous activity were detected by cross-correlation analysis of spontaneous activity and a 3-frame whisker response template that exceeded threshold criteria (see Methods). The detected whisker-evoked-like spontaneous events were then aligned by the start of the template and averaged to make the movie. (AVI 1680 kb)

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Mohajerani, M., Chan, A., Mohsenvand, M. et al. Spontaneous cortical activity alternates between motifs defined by regional axonal projections. Nat Neurosci 16, 1426–1435 (2013). https://doi.org/10.1038/nn.3499

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