LncRNA Dleu2 regulates fear extinction memory through Celf2-driven synaptic plasticity.

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Long noncoding RNAs (lncRNAs) are key regulators of brain function.
• The role of lncRNAs in fear extinction memory is not well understood.

Purpose of the Study:

• To investigate the role of lncRNAs in fear extinction memory.
• To identify specific lncRNAs involved in this process and elucidate their mechanisms.

Main Methods:

• RNA capture sequencing in the infralimbic prefrontal cortex (ILPFC).
• Antisense oligonucleotide (ASO)-mediated knockdown of Dleu2.
• Chromatin Interaction Analysis by Paired-End Tag sequencing (CHIRP-seq) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq).
• Celf2 knockdown and assessment of dendritic spine density.

Main Results:

• Identified Dleu2 as a processed-transcript lncRNA involved in fear extinction.
• Dleu2 knockdown impaired extinction memory, highlighting its essential role.
• Dleu2 binds to the intronic region of Celf2, enhancing its transcription and chromatin accessibility.
• Celf2 knockdown in ILPFC mimicked extinction deficits and reduced dendritic spine number.

Conclusions:

• lncRNA Dleu2 plays a critical role in fear extinction memory by regulating Celf2 expression.
• This mechanism involves modulating chromatin accessibility and promoting Celf2 transcription, impacting synaptic plasticity.
• Dleu2 represents a potential therapeutic target for memory-related disorders.