The Locus Coeruleus Is a Complex and Differentiated Neuromodulatory System

Abstract

Diffuse projections of locus coeruleus (LC) neurons and evidence of synchronous spiking have long been perceived as features of global neuromodulation. Recent studies demonstrated the possibility of targeted modulation by subsets of LC neurons. Non-global neuromodulation depends on target specificity and the differentiated spatiotemporal dynamics within LC. Here, we characterized interactions between 3,164 LC cell pairs in the rat LC under urethane anesthesia. Spike count correlations were near zero and only a small proportion of unit pairs had synchronized spontaneous (15%) or evoked (16%) discharge. We identified infra-slow (0.01-1 Hz) fluctuations of LC unit spike rate, which were also asynchronous across the population. Despite overall sparse population synchrony, we report the existence of LC ensembles and relate them to forebrain projection targets. We also show that spike waveform width was related to ensemble membership, propensity for synchronization, and interactions with cortex. Our findings suggest a partly differentiated and target-specific noradrenergic signal.

Keywords: cross-correlogram; ensemble; gap junction; infra-slow oscillation; locus coeruleus; neuromodulation; noise correlation; noradrenaline; slow wave; synchrony.