Mapping the Brain-Wide Network Effects by Optogenetic Activation of the Corpus Callosum

Abstract

Optogenetically driven manipulation of circuit-specific activity enables causality studies, but its global brain-wide effect is rarely reported. Here, we applied simultaneous functional magnetic resonance imaging (fMRI) and calcium recording with optogenetic activation of the corpus callosum (CC) connecting barrel cortices (BC). Robust positive BOLD was detected in the ipsilateral BC due to antidromic activity, spreading to the ipsilateral motor cortex (MC), and posterior thalamus (PO). In the orthodromic target, positive BOLD was reliably evoked by 2 Hz light pulses, whereas 40 Hz light pulses led to reduced calcium, indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light pulses with whisker stimulation at varied interstimulus intervals. Whisker-induced positive BOLD and calcium signals were reduced at intervals of 50/100 ms. The calcium-amplitude-modulation-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC, ipsilateral MC, and PO. This work raises the need for fMRI to elucidate the brain-wide network activation in response to optogenetic stimulation.

Profiling the transcallosal response of rat motor cortex evoked by contralateral optogenetic stimulation of glutamatergic cortical neurons

“…The cortical LFP responses elicited by optogenetic stimulation of glutamatergic transcallosal projections are in good agreement with previous optogenetic studies in rodents [25,27,37]. Using transgene rats with ubiquitous ChR2 expression, Saiki et al [25] performed cortical optogenetic stimulation of M1 and recorded transcallosally evoked single-unit activity in contralateral M1 at a mean latency of 5.2 ms.…”

“…Transcallosal interhemispheric signal conduction has also been probed with optogenetic stimulation of the somatosensory [26] and barrel cortex [27,37]. Iordanova et al [26] targeted specifically the glutamatergic neurons in the right somatosensory cortex and recorded the optogenetically evoked transcallosal response using silicon probes with linear electrode arrangement.…”

“…Depth profiling of the LFP response showed that the polarity of the first LFP component flips with increasing depth of recording with an initial P1 peak emerging at deeper intracortical recording sites [26]. Chen et al [27] recorded the transcallosally evoked responses after optogenetic stimulation of the somatosensory cortex, reporting a transcallosal response latency of approximately 8.1 ms. Böhm et al [37] performed epicranial optogenetic stimulation above the barrel cortex in mice, and recorded epicranial responses in multiple areas.…”

“…The advent of opto- [19,20] and pharmacogenetic [21,22] tools to selectively stimulate a distinct class of brain cells has massively expanded the potential of studying the CC and its function in animals -both in vitro [23] and in vivo [24][25][26][27]. Optogenetic stimulation of the transcallosal somatosensory or motor projections provides a powerful tool to study the causal significance of the corpus callosum in interhemispheric sensorimotor integration.…”

“…But appropriate use of optogenetic interventions requires detailed knowledge about the stimulusresponse relationship between the stimulation variables and the evoked neuronal response in the contralateral hemisphere. Recent optogenetic studies in rodents and nonhuman primates emphasize that the stimulation induced neuronal activity in the brain, such as the size of the evoked local field potential (LFP) or the change in axonal firing rates, depends on the stimulation variables, such as the stimulation intensity applied or the duration of laser stimulation [25,27,28]. Although the impact of key variables might have been investigated systematically beforehand in many optogenetic stimulation studies, it often remains unclear why a specific set of stimulation variables was used for optogenetic stimulation.…”