Abstract
We have mapped intracortical activity in vivo independent of sensory input using arbitrary point channelrhodopsin-2 (ChR2) stimulation and regional voltage sensitive dye imaging in B6.Cg-Tg (Thy1-COP4/EYFP)18Gfng/J transgenic mice. Photostimulation of subsets of deep layer pyramidal neurons within forelimb, barrel, or visual primary sensory cortex led to downstream cortical maps that were dependent on synaptic transmission and were similar to peripheral sensory stimulation. ChR2-evoked maps confirmed homotopic connections between hemispheres and intracortical sensory and motor cortex connections. This ability of optogentically activated subpopulations of neurons to drive appropriate downstream maps suggests that mechanisms exist to allow prototypical cortical maps to self-assemble from the stimulation of neuronal subsets. Using this principle of map self-assembly, we employed ChR2 point stimulation to map connections between cortical areas that are not selectively activated by peripheral sensory stimulation or behavior. Representing the functional cortical regions as network nodes, we identified asymmetrical connection weights in individual nodes and identified the parietal association area as a network hub. Furthermore, we found that the strength of reciprocal intracortical connections between primary and secondary sensory areas are unequal, with connections from primary to secondary sensory areas being stronger than the reciprocal.
Highlights
Functional relationships between brain areas have been deduced through an elegant combination of structural, electrophysiological, and lesion/inactivation studies (Shepherd et al, 2005; Douglas and Martin, 2007)
If photostimulation was targeted to the left hemisphere HLS1, the data from the center of the left hemisphere HLS1 was not used for regions of interest (ROI) quantification, but the spread of activity within the photostimulated hemisphere and transcallosal responses in the opposite hemisphere were measured
Using the average of photostimulation trials that were normalized to unstimulated trials, we found that a 1 ms electrical stimulation to the right hindlimb led to a localized voltage sensitive dyes (VSD) response at the left hemisphere HLS1 and a discrete activation at the homotopic HLS1 in the right hemisphere (Figure 2A, i)
Summary
Functional relationships between brain areas have been deduced through an elegant combination of structural, electrophysiological, and lesion/inactivation studies (Shepherd et al, 2005; Douglas and Martin, 2007). Functional mapping between specific sites has been performed in vivo through electrical microstimulation (Ferezou et al, 2007; Histed et al, 2009), and combining optogenetic stimulation with functional magnetic resonance imaging (fMRI; Lee et al, 2010; Logothetis et al, 2010; Desai et al, 2011; Kahn et al, 2011), yet electrical microstimulation is limited in the number of regions that can be sampled quickly, and fMRI has limited temporal resolution With these limitations in mind, our goal was to develop an approach that would allow for arbitrary point functional mapping in vivo while maintaining relatively high spatiotemporal resolution
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