Molecular and neural basis of contagious itch behavior in mice

Abstract

Socially contagious itch is ubiquitous in human society, but whether it exists in rodents is unclear. Using a behavioral paradigm that does not entail prior training or reward, we found that mice scratched after observing a conspecific scratching. Molecular mapping showed increased neuronal activity in the suprachiasmatic nucleus (SCN) of the hypothalamus of mice that displayed contagious scratching. Ablation of gastrin-releasing peptide receptor (GRPR) or GRPR neurons in the SCN abolished contagious scratching behavior, which was recapitulated by chemogenetic inhibition of SCN GRP neurons. Activation of SCN GRP/GRPR neurons evoked scratching behavior. These data demonstrate that GRP-GRPR signaling is necessary and sufficient for transmitting contagious itch information in the SCN. The findings may have implications for our understanding of neural circuits that control socially contagious behaviors.

Comment on “Molecular and neural basis of contagious itch behavior in mice”

“…Despite using mice of the same strain, age, sex, and supplier as in (7), we found no evidence for itch contagion in mice using either their definition of imitative scratching or other, less stringent, definitions. Nonetheless, a few methodological differences between the studies should be mentioned.…”

“…Using a newly developed chronic itch mouse model characterized by excessive scratching, Yu et al . (7) recently reported the first evidence for contagious itch in mice observing these BRAF NaV1.8+/+ demonstrators (7, 8). In an independent line of research using the well-characterized histamine model, our group has also investigated contagious itch in mice observing more moderate levels of scratching.…”

“…Using the identical imitative “look-and-scratch” definition described in (7), none of 12 uninjected observers of histamine-injected demonstrators exhibited scratching behavior within 5 s of looking in the direction of the scratching demonstrator (Fig. 2A).…”

“…For example, the mice used in (7) were tested in their home cages, whereas we used an observation box to which the mice were previously habituated. Also, whereas a 60-min test duration was used in (7), we used a 30-min duration due to the acute nature of histamine-induced scratching behavior (9, 10). However, it should be noted that Yu et al reported that most scratching occurred before the 30-min mark and no scratching occurred after the 40-min mark.…”

“…A scratching bout in uninjected mice was defined as lifting of either hind limb to scratch at the face, neck, or side and replacing the paw onto the floor, regardless of the number of scratching strokes that occurred between the first lift and final lowering of the hind limb. Three different analysis strategies were used to assess contagious itch in uninjected observers: 1) bouts of imitative scratching, identical to the “look-and-scratch” method described in (7), where the observer scratches within 5 s of having paused (~1 s) and looked toward the demonstrator scratching; 2) temporally contiguous scratching, where the observer scratches within 30 s of the demonstrator scratching, without regard for “look-and-scratch” behavior; and 3) total scratching bouts during the 30-min observation period (Fig. 1).…”