NEURAL SUBSTRATES OF SOCIAL HIGHER-ORDER LEARNING

Adapting behavior based on context and past experience is essential for social animals. Through higher-order conditioning, also known as mediated learning (ML), animals can associate low-salience sensory cues (conditioned stimuli, CS), such as sounds or lights, with salient events (unconditioned stimuli, US). While recent studies implicate the hippocampus (HPC) and basolateral amygdala (BLA) in ML, how these regions interact with other socially relevant areas, such as the orbitofrontal cortex (OFC), and which cell types are involved remain largely unknown. Moreover, behavioral paradigms specifically designed to study socially induced ML are currently lacking. This project aims to investigate the neural mechanisms underlying higher-order conditioning driven by social cues, focusing on a network including the OFC, BLA, and HPC. To this end, we developed a novel behavioral paradigm in male mice in which a low-salience light and tone are first associated during a preconditioning phase. The light is then devalued by pairing it with a social defeat experience. Direct and mediated learning are subsequently assessed by presenting either the light or the tone in a novel context. Using unsupervised behavioral analysis tools (DeepLabCut, Keypoint MoSeq), we show that mice associate both the light (direct learning) and the tone (ML) with social defeat. Fiber photometry recordings further reveal increased activity of excitatory neurons in the BLA and OFC in response to both cues after conditioning. Overall, this work provides new tools to study socially induced higher-order conditioning and advances our understanding of how social experiences shape behavior.