Input-specific regulation of locus coeruleus activity for mouse maternal behavior

The locus coeruleus (LC) is a small brainstem nucleus that provides the forebrain with the primary source of noradrenaline (NA), a neuromodulator important for a range of core behavioral and physiological functions (Aston-Jones & Cohen, 2005; Martins & Froemke, 2015; Poe et al., 2020). While early theories described the LC as a homogeneous structure whose neurons release NA uniformly to broadly coordinate brain states, recent studies have begun to reveal that complex behavioral contexts can lead to engagement of specific subpopulations of LC neurons depending on their inputs, outputs, and molecular properties (Aston-Jones & Cohen, 2005; Schwarz et al., 2015; Uematsu et al., 2017). Maternal care involves a complex set of behaviors requiring noradrenaline, but whose regulation by LC circuits is unknown (Thomas & Palmiter, 1997). Here we show that LC-NA activity is required for pup retrieval, a rodent parental behavior wherein experienced caretakers retrieve isolated pups back to the nest (Carcea et al., 2021). We demonstrate that pup cues activate LC neurons in maternal female mice- electrophysiological recordings showed that ultrasonic pup vocalizations increased LC firing, and fiber photometry showed that pup contact produced phasic increases in LC-NA activity during retrieval. We then investigated what inputs drive LC activity during maternal behavior, finding a role for a corticotropin-releasing factor (CRF)-positive projection from the central amygdala (CeA) in modulating retrieval. Selective suppression of CeA inputs impaired different facets of retrieval compared to global inhibition of LC-NA neurons. Collectively, our results indicate that input-specific subpopulations of LC neurons coordinate different aspects of neural and behavioral responses for maternal care.