Work

Neurexin regulates mechanical nociceptive sensitization by central inhibition in Drosophila

Year: 2025

Type: article

Abstract: Synaptic adhesion molecules play a crucial role in shaping neural circuits and behavior, yet their contribution to nociceptive processing remains poorly understood. Here, we investigate how the synaptic organizer Neurexin regulates mechanical nociception in Drosophila larvae. Using genetic, behavioral, and circuit-level analyses, we demonstrate that loss of neurexin induces mechanical nociceptive sensitization, which depends on a specific cluster of central cholinergic neurons in the subesophageal zone. These neurons drive sensitization through a C4da-Goro circuit, where Neurexin modulates presynaptic GABA B receptor signaling to control nociceptive excitability. Our findings establish Neurexin as a key of nociceptive sensitization and uncover a synaptic mechanism for tuning nociceptive thresholds, with implications for understanding chronic pain and sensory circuit dysfunctions in neurodevelopmental disorders.

Source: Science Advances

DOI: 10.1126/sciadv.adz9682