痒觉的中枢环路机制

Central Circuitry Mechanisms of Itch Sensation

痒觉是一种诱发抓挠行为的不愉快的感受。近年来,我们对痒觉信息在脊髓水平处理的分子和细胞机制已经有了较为深入的认识。然而,痒觉信息如何从脊髓传递到大脑并不清楚。我们发现,在痒觉诱发抓挠的过程中,脊髓中投射到臂旁核的神经元被激活,光遗传学抑制这条环路的活性可以减少痒觉诱发的抓挠行为。脊髓中痒觉特异的胃泌素释放肽受体阳性神经元与投射到臂旁核的脊髓投射神经元形成兴奋性突触连接。我们进一步研究了臂旁核在痒觉行为过程中的活性变化和功能。我们发现,臂旁核神经元的兴奋性与痒觉诱发的抓挠过程具有很强的相关性。整体抑制臂旁核神经元的活性或者选择性阻断兴奋性神经元的突触传递可以显著降低急性痒引起的抓挠行为,并减缓慢性痒模型的建立。我们的工作揭示了痒觉从脊髓传递到大脑的一条重要环路,并且提示臂旁核是参与痒觉信息处理的重要脑区。该研究为深入阐明痒觉信息加工的脑内环路机制提供了重要基础。

Itch, or pruritus, is an unpleasant cutaneous sensation that triggers scratching behaviors. Much progress has been made in understanding the molecular and cellular mechanisms of itch at the spinal level. However, how itch information is transmitted to the brain and what central circuits underlie the itch-induced scratching behavior remain largely unknown. We found that the spinoparabrachial pathway was activated during itch processing, and that optogenetic suppression of this pathway impaired itch-induced scratching behaviors. Itch-mediating spinal neurons, which express the gastrin-releasing peptide receptor（GRPR）, are di-synaptically connected to parabrachial nucleus（PBN） via glutamatergic spinal projection neurons. In addition, we confirmed the functional role of PBN in itch processing. We found that the activity of PBN neurons was elevated during itch processing. At behavioral level, inhibition of the PBN neurons or blockade of synaptic release of glutamatergic neurons in the PBN suppressed pruritogen-induced scratching behavior and relieved chronic itch, suggesting that PBN is important for itch processing. In summary, we demonstrated that the spinoparabrachial pathway plays a key role in transmitting itch signals from the spinal cord to the brain, and identified the PBN as a first central relay for the itch signal processing. Our study paves the way for further dissection of central circuit mechanisms underlying itch sensation.