Glutamatergic Projections from the Basolateral Amygdala to Medial Prefrontal Cortex Contribute to Acute Itch...

Itch refers to an aversive sensation that generates a desire to scratch. The basolateral amygdala (BLA) activity is crucial in driving motivation, sensation, and emotional responses. Excitatory projections from the BLA play a vital role in regulating neuronal activity throughout the brain, including the medial prefrontal cortex (mPFC). Nevertheless, whether the BLA neurons and BLA-mPFC circuit contribute to itch sensation remains elusive. In this study, fluoro-gold retrograde tracing, morphological staining, and neuronal manipulation approaches were employed to investigate the role of BLA-mPFC projections in itch processing. Results showed that glutamatergic neurons in the BLA were activated in response to histamine- and chloroquine-induced acute itch stimuli. Chemogenetic activation of these neurons significantly mitigated the scratching behavior, whereas their inhibition increased the number of scratching bouts. The percentages of fluoro-gold-labeled CaMKII⁺ neurons expressing FOS in the BLA, which project to the mPFC, were 40.10 ± 2.26% and 73.84 ± 6.48% in acute itch models induced by histamine and chloroquine, respectively. Optogenetic activation of the BLA-mPFC pathway reduced histamine- or chloroquine-induced scratching bouts, whereas its inhibition increased the scratching bouts. These results provide evidence that BLA-mPFC projections are implicated in the acute itch processing, expanding our understanding to the circuit mechanism underlying the modulation of itch.