Precise and Pervasive Phasic Bursting in Locus Coeruleus during Maternal Behavior in Mice.

Abstract

The noradrenergic locus coeruleus (LC) mediates key aspects of arousal, memory, and cognition in structured tasks, but its contribution to naturalistic behavior remains unclear. LC activity is thought to multiplex distinct signals by superimposing sustained ("tonic") firing patterns reflecting global brain states, such as arousal and anxiety, and rapidly fluctuating ("phasic") bursts signaling discrete behaviorally significant events. Manipulations of the LC noradrenergic system broadly impair social behavior, but the temporal structure of LC firing and its relationship to social interaction is unknown. One possibility is that tonic firing may increase in the presence of social partners; it is also possible that phasic bursts may accompany specific social events. We used chronic in vivo electrophysiology and fiber photometry to measure single-unit and population neural activity in LC of freely behaving mice during their interactions with pups. We find that pup retrieval elicits remarkably precise phasic activity in LC that cannot be attributed merely to sensory stimuli, motor activity, or reward. Correlation of LC activity with retrieval events shows that phasic events are most closely related to specific subsequent behaviors. The reliability and magnitude of phasic responses strongly suggest that these events are coordinated across LC and broadcast noradrenaline (NA) release throughout the brain. We also observed slow changes in tonic firing when females performed distinct maternal behaviors such as nest building and pup grooming. We therefore propose that LC signals state changes during sustained interactions and contributes to goal-directed action selection during social behavior with globally broadcast NA release.SIGNIFICANCE STATEMENT Locus coeruleus (LC) releases noradrenaline (NA) brain wide, influencing many cognitive, emotional, and physiological processes. Multifunctionality of LC is maintained by multiplexing NA signaling via brief "phasic" patterns of bursting and slowly changing "tonic" firing. Manipulations of NA impair social behavior, yet the structure of LC activity with respect to specific social events is unknown. We measured LC activity in mice freely interacting with pups. We find that pup retrieval elicits precisely timed and pervasive phasic activation of LC that anticipates specific behaviors. We also found that LC neurons exhibited slow fluctuations in firing during sustained behaviors. We propose that LC simultaneously contributes to goal-directed social action selection with globally broadcast NA release and signals social state changes with increased tonic firing.