Tracing of noradrenergic projections using XXXX -enhanced MRI.

@entity13718 @entity3281 @entity921 @entity35
We examined the applicability of @entity921 -enhanced MRI (MEMRI) to the in vivo tracing of diffuse neuromodulatory projections by means of simultaneous iontophoretic injections of an extremely low, non-toxic concentration of @entity13718 (10mM) and fluorescent dextran in the locus coeruleus (LC) in the @entity35 . We validated the use of the iontophoretic injection by reproducing previously reported results from pressure injections of @entity13718 in primary somatosensory cortex. Twenty fourhours after injection in LC, @entity3281 labeling was detected in major cortical and subcortical targets of LC projections including predominantly ipsilateral primary motor and somatosensory cortices, hippocampus and amygdala. Although the injections were in most cases centered in the core of LC, the pattern of @entity3281 labeling greatly varied across @entity35 . In addition, despite a certain degree of overlap of the labeling obtained with both MEMRI and classical tracing, MEMRI tracing consistently failed to reliably label not only several minor but also major targets of LC, notably the thalamus. The lack of @entity3281 labeling in thalamus possibly reflected a weaker functional connectivity within coeruleothalamic projections that could not be predicted by anatomical tracing. Inversely, a number of brain regions, particularly contralateral motor cortex, that were not or only sparsely labeled with fluorescent dextran were strongly labeled by @entity3281 . This discrepancy could be partly due to both the activity-dependent and transsynaptic nature of @entity3281 transport. The overall labeling produced using MEMRI with iontophoretic injections in LC indicates that the @entity3281 imaging of highly diffuse projections is in principle feasible. However, the labeling pattern of each individual case needs to be carefully interpreted particularly before submitting data for group analysis or in the case of longitudinal examination of discrete changes in functional connectivity under various physiological or behavioral conditions.
