2026 ECNP Congress

PS03-3256

The extended amygdala as a hub for social valence: anatomical connectivity and stress-induced alterations in mice

Alessandra Monaco — F. Fermani, S. Chang · University of Regensburg, Department of Behavioural and Molecular Neurobiology, Regensburg, Germany

2026 ECNP Congress

Social interactions are fundamental components of animal behavior, yet the complex neural mechanisms that encode their valence remain poorly understood [1]. The interstitial nucleus of the posterior limb of the anterior commissure, lateral part (IPACL), a region of the extended amygdala, has recently emerged as a candidate hub for integrating social and emotional information, with neural activity in this area showing strong correlations with both social interactions and anxiety behavior [2]. However, the role of IPACL in shaping social valence and the circuits through which it influences social behavior remain largely unexplored, representing a critical gap in our understanding of the neural basis of social experiences.

To address this gap, we utilized the vGATE system [3], an activity-dependent neuronal labelling approach to map IPACL connectivity in C57BL/6 mice during distinct social encounters, including interactions with same-strain and different-strain conspecifics. Social behavior was evaluated using the Conditioned Place Preference (CPP) paradigm and a free social interaction test quantified via automated pose-estimation (DeepLabCut and DeepOF).

Baseline behavioral analyses revealed no significant behavioral differences between encounter types, providing a controlled framework for the subsequent circuit-level investigation of IPACL’s role in shaping social valence. To investigate how social stressors alter social behavior, mice were subjected to a 21-day Chronic Social Defeat Stress (CSDS) paradigm, in which experimental mice were daily exposed to a novel aggressive CD1 resident for 5 minutes and subsequently housed in the same cage separated by a perforated divider until the following day. Following CSDS, mice exhibited a generalized reduction in social interaction regardless of the conspecific’s strain. Notably, CPP analyses demonstrated that stressed mice shifted their place preference only when conditioned with a non-aggressive CD1 mouse. Moreover, free social interaction analyses revealed that stressed mice showed no significant changes in social behavior toward same-strain conspecifics, neither in total interaction time nor frequency. In contrast, when exposed to a non-aggressive CD1 mouse after CSDS, stressed animals displayed a significant reduction in both total interaction time and interaction frequency. Taking together, these results indicate that CSDS selectively modulates the motivational response to specific social targets.

Further, vGATE-based connectivity mapping revealed a stress-induced reorganization of IPACL circuits, characterized by differential changes in neuronal projections to target regions, pointing to a remodeling of the extended amygdala connectivity that needs further investigation. To assess brain-wide neuronal activation, whole-brain c-Fos quantification was performed 90 minutes after the free social interaction test: since no significant differences in c-Fos expression were detected across conditions, these stress-induced alterations may operate through changes in synaptic strength or excitability rather than large-scale shifts in neuronal activation.

Building upon established IPACL connectivity, these findings provide a characterization of its stress-induced reorganization, revealing how chronic stress selectively alters the neural processing of social valence at circuit level, laying the groundwork for future investigations aimed at finding neuronal subpopulations within IPACL and establishing its causal role in social valence processing.

References

  1. Padilla-Coreano N, Tye KM, Zelikowsky M. Dynamic influences on the neural encoding of social valence. Nat Rev Neurosci. 2022;23(9):535-550. doi:10.1038/s41583-022-00609-1
  2. Chang S, Fermani F, Lao CL, et al. Tripartite extended amygdala-basal ganglia CRH circuit drives locomotor activation and avoidance behavior. Sci Adv. 2022;8(46):eabo1023. doi:10.1126/sciadv.abo1023
  3. Hasan MT, Althammer F, Silva da Gouveia M, et al. A Fear Memory Engram and Its Plasticity in the Hypothalamic Oxytocin System. Neuron. 2019;103(1):133-146.e8. doi:10.1016/j.neuron.2019.04.029