Figure 1.

Optogenetic fMRI. Neural activation of layer V ChR2-expressing neurons by light stimulation evokes a reliable fMRI response that is equivalent to somatosensory response evoked by vibrissa deflection. A, Opto-fMRI experimental design. Atlas (Paxinos and Franklin, 2001) sagittal (i) and coronal (ii) sections depict the placement of the fiber optic (blue line) over primary somatosensory cortex (SI) barrel field. Monte Carlo simulation of laser intensity contours are plotted (iii), demonstrating that light intensity at 750 μm was 10%, power sufficient to induce action potentials in layer V pyramidal neurons in vitro. MI, Primary motor cortex. B, Wide-field fluorescence depicts ChR2 expression of primarily layer V pyramidal neurons in a transgenic Thy1-ChR2-YFP mouse. Sagittal slice depicts expression throughout the neocortex, and an atlas section is superimposed on representative histological and anatomical MRI coronal sections, depicting the site of stimulation for a representative animal. C, A characteristic expression is shown demonstrating fluorescence in layer V pyramidal neurons (top). Maximum intensity projection of confocal laser scanning microscopy demonstrates ChR2 expression (bottom). Denoted by white triangles are apical dendrites approaching the surface, the cell bodies, and axons. D, “Localizer” runs consisted of 16 repetitions of 15 s light-pulses or deflections of the mystacial vibrissae followed by 15 s of no stimulation. A statistical parametric map of a positive BOLD response to light stimulation (p < 0.05 corrected for multiple comparisons) is overlaid on the average fMRI BOLD image of the sequential cross-sections demonstrating the response for the optical drive in a typical animal (“Optogenetic”). A similar BOLD response was observed to vibrissa deflections (“Sensory”).