RT Journal Article SR Electronic T1 Monitoring large populations of locus coeruleus neurons reveals the non-global nature of the norepinephrine neuromodulatory system JF bioRxiv FD Cold Spring Harbor Laboratory SP 109710 DO 10.1101/109710 A1 Nelson K. Totah A1 Ricardo M. Neves A1 Stefano Panzeri A1 Nikos K. Logothetis A1 Oxana Eschenko YR 2017 UL http://biorxiv.org/content/early/2017/02/18/109710.abstract AB The non-specific neuromodulation of the forebrain by the noradrenergic locus coeruleus (LC) is a foundation of wide-ranging theories of cognitive and systems neuroscience. The non-specificity is assumed because of the diffuse projections of the nucleus as well as the synchronous spiking of its neurons. Synchrony, however, has never been assessed in a large population of LC cells, i.e. single units, nor has it been systematically related to specificity of their projection targets. Here, we recorded up to 52 single units simultaneously (3164 unit pairs) in the rat LC, and characterized forebrain projection patterns using antidromic stimulation. Two novel unit types were characterized; they differed by waveform shape, firing rate, and propensity for synchronization. Cross-correlation analysis revealed a surprisingly poor correlation between unit spiking; only 13% of unit pairs had response profiles reflecting synchronization due to common synaptic input or gap junctions. While LC unit spikes were phase locked to cortical slow oscillations (< 2 Hz), they did so intermittently, yielding poor population synchronization. A novel infra-slow (0.01-1 Hz) spiking fluctuation was observed in LC units, yet this too was asynchronous across unit pairs. A highly synchronized minority had a stronger tendency for targeted forebrain neuromodulation. Our findings demonstrate that the LC may convey a more complex and differentiated neuromodulatory signal than is widely assumed.