Interactive connections between the claustrum and lateral parabrachial nucleus participate in the regulation of nociceptive information and accompanying negative emotions

Abstract The claustrum (CLA) is a widely connected brain area associated with pain sensation, but the underlying mechanism remains elusive. Here, we demonstrate that the activation of CLA vesicular glutamate transporter-2 (VGluT2) neurons promotes nociceptive and anxiety-like behaviors, whereas parvalbumin (PV) neurons in the core of the CLA inhibit the functional activity of VGluT2 neurons. Morphologically, the VGluT2 neurons in the shell of the CLA reciprocally communicate with the VGluT2 neurons in the lateral parabrachial nucleus (LPB). Manipulation of the LPBVGluT2–CLAVGluT2 pathway, LPBVGluT2–CLAPV pathway and CLA–LPB glutamatergic pathway results in bidirectional modulation of pain and emotions. Pharmacogenetic activation of the LPBVGluT2–CLAVGluT2–LPBVGluT2 circuit facilitates nociception and negative emotions, and vice versa, alleviates hyperalgesia and anxiety-like behaviors. These findings illuminate that the CLA plays a vital role in pain perception and emotional impacts and provide crucial insight to help researchers unveil the functions of the CLA.