Brainstem noradrenergic neurons have diverse activity patterns across species, sex, age, and genotype

The locus coeruleus (LC) brainstem cell group is evolutionarily conserved across vertebrates and influences both mind (cognition) and body (cardiorespiratory, metabolic, and immune functions) by activating in two - putatively distinct - firing patterns. Yet, the degree to which the LC firing rates and patterns are homogenous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.