Abstract Neurons in the locus coeruleus (LC) have been traditionally viewed as a homogenous population. Recent studies are beginning to uncover heterogeneous molecular phenotypes and projection targets in this nucleus, but how such heterogeneity is ultimately manifested in neuronal physiology and function is largely unknown. We took an orthogonal approach to directly assess the physiological and functional heterogeneity in the LC. By identifying noradrenergic neurons using a genetic-based tagging approach, our study revealed a subset of neurons exhibiting a distinctive narrow spike waveform and lacking the prolonged after-hyperpolarization. We further provided evidence establishing a link between the proximity of LC neurons and their response latency, where putatively proximal neurons tended to have a long latency to optogenetic activation. Finally, we found that response latency of LC neurons was correlated with their burst firing and distinct relationship with pupil diameter. Together, our study presents novel evidence to reveal and link LC heterogeneity at the physiological level to that at the functional level.

Physiological and functional heterogeneity in the mouse locus coeruleus