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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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.
The authors declare no competing financial interests.
Supplementary Figures 1-10 (PDF 3997 kb)
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 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)
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)
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)
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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