Emotional modulation of neural and behavioral responses to social cues by locus coeruleus

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PROJECT SUMMARY The goal of this proposal is to define the mechanisms by which noradrenaline (NA) from locus coeruleus (LC) attaches emotional significance to social cues and regulates socially-motivated behavior. Appropriate responses to rewarding stimuli are central to survival. Control of reward-driven behavior is most often associated with midbrain dopamine circuits. Yet, there is mounting evidence that the attractive potency (‘motivational salience’) of a given cue dynamically depends on a broader set of circuits signaling context and internal state. For example, responses to social rewards depend on their emotional significance. Adult female mice undergo dramatic changes in their response to mating and familial cues after their initial sexual and maternal experiences. These powerfully arousing experiences attach enduring emotional significance to social cues experienced during the encounter and increase their motivational salience. LC is a key structure for broadcasting arousal and emotional significance. Past studies strongly suggest that LC activity signals the emotional content of social cues, but due to the limited temporal resolution of the methods used in those studies, it is unclear whether LC affects motivated behavior by altering neural responses to social stimuli or by promoting specific behaviors. Here we propose to use high temporal resolution methods for recording neural activity, that have never before been performed in LC of animals freely engaging in social behavior. We will answer the question of whether LC spiking occurs predominantly in response to social sensory cues or in advance of behavioral choices. Our central hypothesis is that LC shapes social goal-directed behavior both by modulating the motivational salience of social cues and facilitating behavior responses. We aim to answer three outstanding questions regarding the contribution of LC activity to social behavior: (1) What is the timing of activity LC relative to social behaviors, and does it change with social experience? (2) How do tonic (sustained) activity and phasic (brief) activity contribute to behavior? and (3) How does LC input to downstream targets affect neural activity and behavioral responses. LC has long been indirectly implicated in the regulation of social behavior, but its specific online contribution to social interactions is not known. The significance of these studies lies in their potential to clarify this aspect of LC function and reconcile it with LC’s other roles in cognition, learning and control of arousal state.