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

Abstract

Abstract Whole-brain intrinsic activity as detected by resting-state fMRI can be summarized by three primary spatiotemporal patterns. These patterns have been shown to change with different brain states, especially arousal. The noradrenergic locus coeruleus (LC) is a key node in arousal circuits and has extensive projections throughout the brain, giving it neuromodulatory influence over the coordinated activity of structurally separated regions. In this study, we used optogenetic-fMRI in rats to investigate the impact of LC stimulation on the global signal and three primary spatiotemporal patterns. We report small, spatially specific changes in global signal distribution as a result of tonic LC stimulation, as well as regional changes in spatiotemporal patterns of activity at 5 Hz tonic and 15 Hz phasic stimulation. We also found that LC stimulation had little to no effect on the spatiotemporal patterns detected by complex principal component analysis. We hypothesize that localized effects could be due to engagement of LC modules that support behaviors induced by our specific stimulation parameters, in addition to noradrenergic receptor profile distributions. Nonetheless, these results show that the effects of LC activity on the BOLD signal in rats may be small and regionally concentrated, as opposed to widespread and globally acting, further supporting emerging evidence of a modular LC.