The effects of locus coeruleus optogenetic stimulation on global spatiotemporal patterns in rats

Whole-brain intrinsic activity as detected by resting-state fMRI can besummarized by three primary spatiotemporal patterns. These patterns have beenshown to change with different brain states, especially arousal. Thenoradrenergic locus coeruleus (LC) is a key node in arousal circuits and hasextensive projections throughout the brain, giving it neuromodulatory influenceover the coordinated activity of structurally separated regions. In this study,we used optogenetic-fMRI in rats to investigate the impact of LC stimulation onthe global signal and three primary spatiotemporal patterns. We report small,spatially specific changes in global signal distribution as a result of tonic LCstimulation, as well as regional changes in spatiotemporal patterns of activityat 5 Hz tonic and 15 Hz phasic stimulation. We also found that LC stimulationhad little to no effect on the spatiotemporal patterns detected by complexprincipal component analysis. We hypothesize that localized effects could be dueto engagement of LC modules that support behaviors induced by our specificstimulation parameters, in addition to noradrenergic receptor profiledistributions. Nonetheless, these results show that the effects of LC activityon the BOLD signal in rats may be small and regionally concentrated, as opposedto widespread and globally acting, further supporting emerging evidence of amodular LC.