Cortical representation of pain by stable dedicated neurons and dynamic ensembles

The perception of pain arises from distributed brain activity triggered by noxious stimuli. However, which patterns of activity make nociception distinct from other salient sensory experiences is still unknown. Using in vivo chronic two-photon calcium imaging in slightly anaesthetized mice, we identified a nociception-specific representation in the anterior cingulate cortex (ACC), that is attained by a core of neurons that code for a generalized concept of the pain experience. The overall ensemble activity allowed for an efficient discrimination of the sensory space, despite a drift in single-neuron sensory tuning over time. Following sciatic nerve lesion, the representation of nociceptive stimuli was impaired as a consequence of innocuous stimuli expanded into the nociception-specific ensemble, leading to a dysfunctional discrimination of sensory events in the ACC. Thus, the hallmark of chronic pain at the cortical neuronal network level is an impairment of pattern separation and classification identifying a circuit mechanism for altered pain processing in the brain. ### Competing Interest Statement The authors have declared no competing interest.