scholarly journals The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory

2011 ◽  
Vol 14 (9) ◽  
pp. 1115-1117 ◽  
Author(s):  
Quan Lin ◽  
Wei Wei ◽  
Carlos M Coelho ◽  
Xiang Li ◽  
Danay Baker-Andresen ◽  
...  
Keyword(s):  
Fear Extinction ◽  
Extinction Memory ◽  
The Brain

scholarly journals The accumulation of N6-methyl-2’-deoxyadenosine in DNA drives activity-induced gene expression and is required for the extinction of conditioned fear

2016 ◽  
Author(s):  
Xiang Li ◽  
Qiongyi Zhao ◽  
Wei Wei ◽  
Quan Lin ◽  
Christophe Magnan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cortical Neurons ◽  
Conditioned Fear ◽  
Fear Extinction ◽  
Adult Brain ◽  
Extinction Learning ◽  
Prefrontal Cortical ◽  
Genome Wide ◽  
Extinction Memory ◽  
The Brain

Here we report that the recently discovered mammalian DNA modification N6-methyl-2’-deoxyadenosine (m6dA) is dynamically regulated in primary cortical neurons, and accumulates along promoters and coding sequences within the genome of activated prefrontal cortical neurons of adult C57/BI6 mice in response to fear extinction learning. The deposition of m6dA is generally associated with increased genome-wide occupancy of the mammalian m6dA methyltransferase, N6amt1, and this correlates with fear extinction learning-induced gene expression. Of particular relevance for fear extinction memory, the accumulation of m6dA is associated with an active chromatin state and the recruitment of transcriptional machinery to the brain-derived neurotrophic factor (Bdnf) P4 promoter, which is required for Bdnf exon IV mRNA expression and for the extinction of conditioned fear. These results expand the scope of DNA modifications in the adult brain and highlight changes in m6dA as a novel neuroepigenetic mechanism associated with activity-induced gene expression and the formation of fear extinction memory.

scholarly journals The role of carbonic anhydrases in extinction of contextual fear memory

2020 ◽  
Vol 117 (27) ◽  
pp. 16000-16008 ◽  
Author(s):  
Scheila Daiane Schmidt ◽  
Alessia Costa ◽  
Barbara Rani ◽  
Eduarda Godfried Nachtigall ◽  
Maria Beatrice Passani ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Fear Conditioning ◽  
Fear Extinction ◽  
Systemic Administration ◽  
Contextual Fear Conditioning ◽  
Ventromedial Prefrontal Cortex ◽  
Carbonic Anhydrases ◽  
Contextual Fear ◽  
Extinction Memory ◽  
The Brain

Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in mammals with 16 isoforms that differ in terms of catalytic activity as well as cellular and tissue distribution. CAs catalyze the conversion of CO2to bicarbonate and protons and are involved in various physiological processes, including learning and memory. Here we report that the integrity of CA activity in the brain is necessary for the consolidation of fear extinction memory. We found that systemic administration of acetazolamide, a CA inhibitor, immediately after the extinction session dose-dependently impaired the consolidation of fear extinction memory of rats trained in contextual fear conditioning.d-phenylalanine, a CA activator, displayed an opposite action, whereas C18, a membrane-impermeable CA inhibitor that is unable to reach the brain tissue, had no effect. Simultaneous administration of acetazolamide fully prevented the procognitive effects ofd-phenylalanine. Whereasd-phenylalanine potentiated extinction, acetazolamide impaired extinction also when infused locally into the ventromedial prefrontal cortex, basolateral amygdala, or hippocampal CA1 region. No effects were observed when acetazolamide ord-phenylalanine was infused locally into the substantia nigra pars compacta. Moreover, systemic administration of acetazolamide immediately after the extinction training session modulated c-Fos expression on a retention test in the ventromedial prefrontal cortex of rats trained in contextual fear conditioning. These findings reveal that the engagement of CAs in some brain regions is essential for providing the brain with the resilience necessary to ensure the consolidation of extinction of emotionally salient events.

Partial and Total Sleep Deprivation Interferes With Neural Correlates of Consolidation of Fear Extinction Memory

2021 ◽  
Vol 89 (9) ◽  
pp. S176
Author(s):  
Jeehye Seo ◽  
Edward F. Pace-Schott ◽  
Mohammed R. Milad ◽  
Huijin Song ◽  
Anne Germain
Keyword(s):  
Sleep Deprivation ◽  
Neural Correlates ◽  
Fear Extinction ◽  
Total Sleep Deprivation ◽  
Extinction Memory

scholarly journals On the discovery of ADRAM, an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3

2021 ◽  
Author(s):  
XIang Li ◽  
Qiongyi Zhao ◽  
Ziqi Wang ◽  
Wei-Siang Liau ◽  
Dean Basic ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Large Population ◽  
Regulation Of Gene Expression ◽  
Fear Extinction ◽  
Early Gene ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Chaperone Protein ◽  
The Brain

Long-noncoding RNA (lncRNA) comprise a new class of genes that have been assigned key roles in development and disease. Many lncRNAs are specifically transcribed in the brain where they regulate the expression of protein-coding genes that underpin neuronal function; however, their role in learning and memory remains largely unexplored. We used RNA Capture-Seq to identify a large population of lncRNAs that are expressed in the infralimbic cortex of adult male mice in response to fear-related learning, with 14.5% of these annotated in the GENCODE database as lncRNAs with no known function. We combined these data with cell-type-specific ATAC-seq on neurons that had been selectively activated by fear-extinction learning, and revealed 434 lncRNAs derived from enhancer regions in the vicinity of protein-coding genes. In particular, we discovered an experience-induced lncRNA called ADRAM that acts as both a scaffold and a combinatorial guide to recruit the brain-enriched chaperone protein 14-3-3 to the promoter of the memory-associated immediate early gene Nr4a2. This leads to the expulsion of histone deactylases 3 and 4, and the recruitment of the histone acetyltransferase creb binding protein, which drives learning-induced Nr4a2 expression. Knockdown of ADRAM disrupts this interaction, blocks the expression of Nr4a2, and ultimately impairs the formation of fear-extinction memory. This study expands the lexicon of experience-dependent lncRNA activity in the brain, highlights enhancer-derived RNAs (eRNAs) as key players in the epigenetic regulation of gene expression associated with fear extinction, and suggests eRNAs, such as ADRAM, may constitute viable targets in developing novel treatments for fear-related anxiety disorders.

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