Challenges and Perspectives of Mapping Locus Coeruleus Activity in the Rodent with High-Resolution fMRI

The locus coeruleus (LC) is one of the most commonly studied brainstem nuclei when investigating brain-behavior associations. The LC serves as a major brainstem relay for both ascending bottom-up and descending top-down projections. Specifically, noradrenergic (NA) LC neurons not only connect globally to higher-order subcortical nuclei and cortex to mediate arousal and attention but also directly project to other brainstem nuclei and to the spinal cord to control autonomic function. Despite the extensive investigation of LC function using electrophysiological recordings and cellular/molecular imaging for both cognitive research and the contribution of LC to different pathological states, the role of neuroimaging to investigate LC function has been restricted. For instance, it remains challenging to identify LC-specific activation with functional MRI (fMRI) in animal models, due to the small size of this nucleus. Here, we discuss the complexity of fMRI applications toward LC activity mapping in mouse brains by highlighting the technological challenges. Further, we introduce a single-vessel fMRI mapping approach to elucidate the vascular specificity of high-resolution fMRI signals coupled to LC activation in the mouse brainstem.