Processing of pain and itch information by modality-specific neurons within the anterior cingulate cortex in mice

Pain and itch are aversive sensations with distinct qualities, processed in overlapping pathways and brain regions, including the anterior cingulate cortex (ACC), which is critical for their affective dimensions. However, the cellular mechanisms underlying their processing in the ACC remain unclear. Here, we identify modality-specific neuronal populations in layer II/III of the ACC in mice involved in pain and itch processing. Using a synapse labeling tool, we show that pain- and itch-related neurons selectively receive synaptic inputs from mediodorsal thalamic neurons activated by pain and itch stimuli, respectively. Chemogenetic inhibition of these neurons reduced pruriception or nociception without affecting the opposite modality. Conversely, activation of these neurons did not enhance stimulus-specific responses but commonly increased freezing-like behavior. These findings reveal that the processing of itch and pain information in the ACC involves activity-dependent and modality-specific neuronal populations, and that pain and itch are processed by functionally distinct ACC neuronal subsets.