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Central Circuitry Mechanisms of Itch Sensation
Mu Di1,2, Sun Yangang1*
1Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences Center for Excellence in Brain Scienceand Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; 2University of Chinese Academy of Sciences, Beijing 100049, China
Abstract: 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.
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.
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