QBI neuroscientists have shed new light on the processes involved in loosening the grip of fear-related memories, particularly those implicated in conditions such as phobias and post-traumatic stress disorder (PTSD).
Dr Timothy Bredy says his team has discovered a previously unrecognised layer of gene regulation associated with fear extinction.
The brain-specific microRNA, MIR-128B, is believed to regulate the formation of fear extinction, an inhibitory learning process thought to be critical for controlling fear-related behaviour when the fear response is no longer required.
Published this month in Nature Neuroscience, the study explores how fear-related memories are formed, updated, and extinguished at the molecular level.
It also provides fresh understanding of the actual function of genes expressed at the time of retrieval of fear memories, and how they are regulated to facilitate fear extinction.
“This is the first demonstration of how small non-coding RNAs contribute to the formation of fear extinction memory, and highlights the adaptive significance of activity-dependent microRNA expression in the adult brain,” Dr Bredy explains.
Non-coding RNAs are believed to function by directing the epigenome to activate or silence genes although the genome itself remains the same.
Small non-coding RNAs, such as the microRNAs studied here, can regulate gene function by complementary binding to the 3’ untranslated end of their protein-coding target genes, resulting in transcriptional silencing.
Dr Bredy points out that the extinction of fear-related memories occurs in the face of a competing memory process called reconsolidation, which sees memories potentially undergo modification every time they are retrieved.
“Contrary to popular belief, fear-related memories are not set in stone,” Dr Bredy says.
“Extinction learning involves retrieval and expression of the original fear memory, which naturally permits either the restabilisation of the original trace, or new extinction learning.
“And in order for new memories to be firmly established, the genes associated with the original fear memory trace must be transiently inhibited, so that the fear extinction process can proceed.”
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NOTES TO THE EDITOR:
Psychiatric Epigenomics Laboratory
Dr Timothy Bredy’s laboratory is interested in elucidating how the genome is connected to the environment, and how this relationship shapes brain and behaviour across the lifespan. Embedded within the chromatin landscape, directly at the interface between intracellular signalling and genomic DNA, epigenetic mechanisms including histone modifications, DNA methylation and non-coding RNA’s represent an attractive foundation for experience-dependent, long-lasting changes in gene expression, cellular function and behaviour. In contrast to the information conveyed by a static genome, the epigenome is very dynamic and can be modified by exposure to a variety of environmental stimuli including fear-related learning, exposure to drugs of abuse, environmental toxins, dietary factors, and social interaction.
Queensland Brain Institute
The Queensland Brain Institute (QBI) was established as a research institute of the University of Queensland in 2003. The Institute is now operating out of a new $63 million state-of-the-art facility and houses 33 principal investigators with strong international reputations. QBI is one of the largest neuroscience institutes in the world dedicated to understanding the mechanisms underlying brain function.