The locus coeruleus is a complex and differentiated neuromodulatory system

Abstract

SummaryUnderstanding the forebrain neuromodulation by the noradrenergic locus coeruleus (LC) is fundamental for cognitive and systems neuroscience. The diffuse projections of individual LC neurons and presumably their synchronous spiking have long been perceived as features of the global nature of noradrenergic neuromodulation. Yet, the commonly referenced “synchrony” underlying global neuromodulation, has never been assessed in a large population, nor has it been related to projection target specificity. Here, we recorded up to 52 single units simultaneously (3164 unit pairs in total) in rat LC and characterized projections by stimulating 15 forebrain sites. Spike count correlations were low and, surprisingly, only 13% of pairwise spike trains had synchronized spontaneous discharge. Notably, even noxious sensory stimulation did not activate the entire population, only evoking synchronized responses in ~16% of units on each trial. We also identified novel infra-slow (0.01-1 Hz) fluctuations of LC unit spiking that were asynchronous across the population. A minority, synchronized possibly by gap junctions, was biased toward restricted (non-global) forebrain projection patterns. Finally, we characterized two types of LC single units differing by waveform shape, propensity for synchronization, and interactions with cortex. These cell types formed finely-structured ensembles. Our findings suggest that the LC conveys a highly complex, differentiated, and potentially target-specific neuromodulatory signal.