NORADRENERGIC MODULATION OF DORSAL HIPPOCAMPAL ACTIVITY DURING PROSOCIAL RESCUE BEHAVIOR IN MICE

Prosocial behaviors, such as rescuing an individual in distress, require the coordinated integration of emotional, cognitive, and motivational processes. Work from our laboratory identified the dorsal hippocampus (dHPC) as essential for the acquisition of a prosocial rescue behavior in mice, in which an “observer” mouse learns to liberate a “victim” conspecific from cold water. However, the neuromodulatory mechanisms supporting rescue learning remain poorly understood. Norepinephrine (NE) is a key regulator of arousal, attention, and synaptic plasticity and has been implicated in social behavior. Yet, how noradrenergic signaling modulates hippocampal activity during tasks involving cognitive and affective demands remains largely unknown. We therefore investigated the real-time dynamics of NE release in the dHPC during the acquisition and expression of rescue behavior. Using fiber photometry together with the genetically encoded NE biosensor GRAB-NE, we monitored hippocampal noradrenergic signaling in freely behaving mice across training. Our findings reveal robust, event-related NE transients aligned with key behavioral milestones, including victim insertion, liberation, and post-liberation social reunion. Importantly, NE dynamics during rescue behavior differ from those observed on non-social control days, suggesting a specific engagement of noradrenergic modulation during prosocial action. Ongoing analyses are characterizing learning-dependent changes across training stages and examining the influence of biological sex on hippocampal NE signaling. Together, these experiments aim to elucidate how noradrenergic modulation shapes hippocampal circuits to support prosocial learning, memory, and social plasticity. Understanding these mechanisms may provide insight into neuropsychiatric disorders marked by impaired social behavior and reduced prosociality.