Neuropeptides in control of left–right neural circuits

Despite extensive research on hemispheric asymmetries, the mechanisms regulating lateralized brain functions are incompletely understood. Growing evidence suggests that lateralized neural circuits are side-specifically controlled, in part, by neuropeptides acting as neuromodulators, paracrine factors, and neurohormones. This review highlights evidence supporting this concept in the contexts of lateralized pain processing in the amygdala, control of auditory signaling, lateralized interoceptive signaling, and side-specific endocrine regulation. Our focus is primarily on rodent studies, with supporting data from humans and nonmammalian species, including turtles and nematodes. Left-right side-specific control may be rooted in a bipartite, lateralized organization of neuropeptide systems. Neuropeptides with asymmetric actions may act locally within specific brain regions or be coordinated across the neuraxis. These findings converge on a model in which neuropeptides enable lateralized control through interconnected mechanisms spanning gene expression, neural circuits, and behavioral outcomes.