Prefrontal engrams of long-term fear memory and pain

This dataset contains electrophysiological spike time data and associated analysis procedures as well as image analysis scripts reported in Stegemann et al. Prefrontal engrams of long-term fear memory perpetuate pain perception. Nature Neuroscience (2023). Abstract: A painful episode can lead to life-long increase in an individual’s experience of pain. Fearful anticipation of imminent pain could play a role in this phenomenon, but the neurobiological underpinnings are unclear, since fear can both suppress and enhance pain. Here, we show in mice that long-term associative fear memory stored in neuronal engrams in the prefrontal cortex (PFC) determines whether a painful episode shapes pain experience later in life. Furthermore, in conditions of inflammatory and neuropathic pain, prefrontal fear engrams expand to encompass neurons representing nociception and tactile sensation, leading to pronounced changes in prefrontal connectivity to fear-relevant brain areas. Conversely, silencing prefrontal fear engrams reverses chronically established hyperalgesia and allodynia. These results reveal that a discrete subset of PFC neurons can account for the debilitating comorbidity of fear and chronic pain and show that attenuating the fear memory of pain can alleviate chronic pain itself.