To Itch or Not to Itch

Yu YQ, Barry DM, Hao Y, Liu XT, Chen ZF. (2017) Molecular and Neural Basis of Contagious Itch Behavior in Mice. Science 355(6329):1072-76. PMID: 28280205

Observing others scratch themselves can make you want to do so.  This contagious itching has been observed in monkeys and humans, but what about rodents?  Yu et al. found that mice do imitate scratching when they observe it in other mice.  The authors identified a brain area called the suprachiasmatic nucleus (SCN) as a key circuit for mediating contagious itch.  Gastrin-releasing peptide and its receptor in the SCN were necessary and sufficient to transmit this contagious behavior.

The authors selectively ablated the SCN gastrin-releasing peptide receptor (GRPR) neurons using Bombesin-SAP (Cat# IT-40), a peptide-conjugated toxin that kills GRPR neurons in the spinal cord.  After bilateral injection of Bombesin-SAP into the SCN, immunohistochemistry showed that Bombesin-SAP injection resulted in ablation of SCN GRPR+ neurons.  The effects of Bombesin-SAP–induced GRPR neuronal ablation were also confirmed by in situ hybridization.  Although control mice exhibited normal imitative scratching behavior as expected, mice treated with Bombesin-SAP in the SCN barely showed imitative scratching behavior.  Bombesin-SAP treatment did not affect the number of look behaviors relative to controls.  There was no difference in acute itch behavior after histamine injection or spontaneous scratches in Bombesin-SAP SCN-treated mice relative to controls.

Figure 1: Ablation or inhibition of GRPR+ or GRP+ neurons in the SCN blocks contagious itch.  (A) Schematic of Bombesin-SAP (BB-sap, 40 ng / 200 nL) bilateral injection into SCN.  (B) Image of GRPR immunohistochemistry in SCN from saline control or BB-sap treated mice.  (C) Mean number of GRPR+ neurons in SCN from saline control or BB-sap treated mice.

The authors found that itch is contagious in mice.  Their results identify a previously unknown function of SCN by revealing its critical role in contagious itch transmission.  Using cell type-specific inhibition and activation, they discovered that SCN GRP/GRPR neurons are key conduits for receiving, integrating, and transmitting visually-induced itch information.  GRP depletion after the contagious itch test supported the idea that GRP is released from GRPergic fibers to activate GRPR+ neurons.  Exogenous GRP-induced scratching behavior is completely abolished in GRPR knockout mice.

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