Mapping the brain-wide network effects by optogenetic activation of the corpus callosum

ABSTRACT The optogenetically driven manipulation of circuit-specific activity enabled functional causality studies in animals, but its global effect on the brain is rarely reported. Here, we applied simultaneous fMRI with calcium recording to map brain-wide activity by optogenetic activation of fibers running in one orientation along the corpus callosum(CC) connecting the barrel cortex(BC). Robust positive BOLD signals were detected in the ipsilateral BC due to antidromic activity, which spread to ipsilateral motor cortex(MC) and posterior thalamus(PO). In the orthodromic target (contralateral barrel cortex), positive BOLD signals were reliably evoked by 2Hz light pulses, whereas 40Hz light pulses led to a reversed sign of BOLD - indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light with peripheral whisker stimulation at varied inter-stimulus intervals. Whisker induced positive BOLD, and calcium signals were reduced at inter-stimulus intervals of 50/100ms. The calcium-amplitude modulation (AM)-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC as well as ipsilateral MC and PO. This work raises the need of fMRI to elucidate the brain-wide network activation in response to projection-specific optogenetic stimulation.