Neuroepigenetic mechanisms underlying fear extinction: emerging concepts

摘要

An understanding of how memory is acquired and how it can be modified in fear-related anxiety disorders, with the enhancement of failing memories on one side and a reduction or elimination of traumatic memories on the other, is a key unmet challenge in the fields of neuroscience and neuropsychiatry. The latter process depends on an important form of learning called fear extinction, where a previously acquired fear-related memory is decoupled from its ability to control behaviour through repeated non-reinforced exposure to the original fear-inducing cue. Although simple in description, fear extinction relies on a complex pattern of brain region and cell-type specific processes, some of which are unique to this form of learning and, for better or worse, contribute to the inherent instability of fear extinction memory. Here, we explore an emerging layer of biology that may compliment and enrich the synapse-centric perspective of fear extinction. As opposed to the more classically defined role of protein synthesis in the formation of fear extinction memory, a neuroepigenetic view of the experience-dependent gene expression involves an appreciation of dynamic changes in the state of the entire cell: from a transient change in plasticity at the level of the synapse, to potentially more persistent long-term effects within the nucleus. A deeper understanding of neuroepigenetic mechanisms and how they influence the formation and maintenance of fear extinction memory has the potential to enable the development of more effective treatment approaches for fear-related neuropsychiatric conditions.