Spontaneous cortical activity alternates between motifs defined by regional axonal projections


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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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.

Author information

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.

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)

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) doi:10.1038/nn.3499

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