INTRODUCTION: Object-directed behavior is essential for survival in natural environments. Although recent research has concentrated on how objects are encoded and egocentric spatial relationships are represented within the lateral entorhinal cortex (LEC), the downstream circuitry and mechanisms governing these behaviors remain largely unknown. Due to its connectivity a potential target could be the amygdala, known for driving defensive and appetitive behaviors; however, understanding how it integrates spatial object information remains challenging.

AIM(S): To address these gaps, we aimed to conduct a comprehensive LEC-amygdala network investigation for its role in object valence encoding and their distances, as well as experience-dependent avoidance behavior using a mouse object-conditioning task.

METHOD(S): We used CTB tracing and object conditioning task with c-fos mapping for a preliminary circuit screen. Next, a projection and/or cell-type-specific Ca2+ imaging and optogenetic manipulation during our behavioral task was used, followed by machine learning modeling of our circuit in driving the relevant behaviors.

RESULTS: We show the complexities of LEC-to-amygdala (BLA and CEl) projections, which are finely tuned to regulate spatial interactions with objects in the environment. These circuits incorporate 2 experience-dependent valence channels, which modulate an ethologically relevant safety mechanism that is crucial for navigating threats amid uncertainty. The balance between these signals exert precise control over object encounters and proximity.

CONCLUSIONS: Together, we propose a comprehensive neuronal circuit framework underlying ethologically relevant behavior and offer a roadmap for future exploration into the intricate interplay between action sequences and object encoding. This not only expands current understandings of LEC-amygdala circuitry function but also sheds light on the transformative process through which object information within the brain network translates into meaningful, directed behavior.

FINANCIAL SUPPORT: W. H. was supported by the European Community’s 7th Framework Programme (FP/2007-2013) / ERC grant no. 311701, the IMP, Boehringer Ingelheim and the FFG.