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Abstract

We examined anterograde labeling of noradrenergic terminals originating from the neurons of brain stem neuromodulatory nucleus Locus Coeruleus (LC), a major course of noradrenaline in the rat forebrain, by means of simultaneous iontophoretic injection of paramagnetic (Mn2 +) and classical (fluorescent dextran) tracers in the LC. Both MEMRI and fluorescent microscopy revealed anterograde labeling in major terminal fields of LC neurons (Swanson and Hartman, 1975; Ungerstedt, 1971) 24 h and 5 d after injection, respectively. Predominantly ipsilateral labeling of thalamic nuclei, primary sensory cortices, medial prefrontal cortex, and olfactory bulbs reflected previously demonstrated monosynaptic projections of the LC neurons in multiple target brain regions. The labeling patterns of both paramagnetic and classical tracers were strikingly similar. Importantly, iontophoretic injection of Mn2+ did not produce neurotoxic effects as there were no signs of neuronal death or glial inflammatory reaction at the injection site 5 days after injection. The reported results further validate MEMRI tract-tracing technique allowing visualization a highly distributed and distal efferent projections arising from the brain stem nucleus. Thus, MEMRI may be used for mapping convergent target brain regions of different neuromodulatory systems in the same animal and their functional reorganization in longitudinal studies.