The bradykinin B2 receptor as a context-dependent modulator of neural circuit function.

The kallikrein-kinin system (KKS) is a proteolytic signaling pathway traditionally associated with vascular regulation and inflammation, but increasing evidence indicates that its components are also expressed in the central nervous system. The bradykinin B2 receptor (B2R), the main mediator of kinin signaling, has been implicated in neuronal differentiation, synaptic modulation, and activity-dependent neuroplasticity. However, its physiological role in neural circuit regulation remains poorly understood. Recent studies using cell-type-specific genetic models suggest that neuronal B2R signaling is largely dispensable for maintaining basal behavioral states. In contrast, growing evidence indicates that B2R plays a more prominent role in glial-mediated inflammatory responses, particularly in astrocytes. Here, we propose that B2R functions as a context-dependent neuromodulatory system that links neuroinflammatory signaling to neural circuit plasticity. Within this framework, B2R activation may become functionally relevant during inflammatory conditions or physiological stimulation, influencing dopaminergic circuits involved in motivation and reward-related behaviors.