Syn-mCherry AAV (Serotype Retrograde)

Acute itch is a protective system that warns the body of the presence of external irritants, whereas chronic itch is a debilitating but poorly treated clinical disorder that results in repetitive scratching and skin damage. Here, researchers identify a cell type-dependent role played by the anterior cingulate cortex (ACC) in controlling chronic itch-associated excessive scratching behavior in mice. Furthermore, researchers describe a neural circuit that originates from excitatory neurons in the ACC and extends to the ventral tegmental area (VTA) that is critically involved in chronic itch. The ACC→VTA circuit also selectively modulates histaminergic acute itch. Finally, ACC neurons were shown to predominantly innervate non-dopaminergic neurons of the VTA. These findings reveal a cortical-midbrain circuit underlying chronic itch-induced scratching behavior and provide new insights for therapeutic intervention.

Previous studies have demonstrated a reciprocal inter-connection between ACC and VTA. Human imaging studies have shown that both regions are involved in itch processing. Therefore, the researchers wondered whether the ACC→VTA projection could be activated by chronic pruritogenic stimuli. To this end, AAV-Retro-hSyn-mCherry was injected into the VTA, and co-staining of c-Fos expression with mCherry was tested 4 weeks later (Figure 3A-C). The total number of mCherry+ neurons in the diphenylcyclopropenone (DCP) group was found to be no different from that in the control group (Figure 3D, E). However, animals treated with DCP had more c-Fos+/mCherry+ neurons (Figure 3F, G). In addition, DCP triggered an increase in the percentage of c-Fos+/mCherry+ neurons in all bregma planes of the ACC (Figure 3H). These data indicate a dramatic activation of the ACC neurons projecting to the VTA under the conditions of chronic itch.

Figure 1. Activation of the ACC→VTA excitatory projection by chronic itch. (Zhang T T, et al., 2023)