Neuroepigenetic mechanisms underlying fear extinction: emerging concepts. 2019

Paul R Marshall, and Timothy W Bredy
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia. paul.marshall@uq.edu.au.

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.

UI MeSH Term Description Entries
D007858 Learning Relatively permanent change in behavior that is the result of past experience or practice. The concept includes the acquisition of knowledge. Phenomenography
D008568 Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D005108 Extinction, Psychological The procedure of presenting the conditioned stimulus without REINFORCEMENT to an organism previously conditioned. It refers also to the diminution of a conditioned response resulting from this procedure. Psychological Extinction,Extinction (Psychology),Extinctions (Psychology),Extinctions, Psychological,Psychological Extinctions
D005239 Fear The affective response to an actual current external danger which subsides with the elimination of the threatening condition. Threat Cues,Threat Sensitivity,Cue, Threat,Fears,Sensitivity, Threat,Threat Cue,Threat Sensitivities
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001523 Mental Disorders Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. Mental Illness,Psychiatric Diseases,Psychiatric Disorders,Psychiatric Illness,Behavior Disorders,Diagnosis, Psychiatric,Mental Disorders, Severe,Psychiatric Diagnosis,Illness, Mental,Mental Disorder,Mental Disorder, Severe,Mental Illnesses,Psychiatric Disease,Psychiatric Disorder,Psychiatric Illnesses,Severe Mental Disorder,Severe Mental Disorders
D044127 Epigenesis, Genetic A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression. Epigenetic Processes,Epigenetic Process,Epigenetics Processes,Genetic Epigenesis,Process, Epigenetic,Processes, Epigenetic,Processes, Epigenetics

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