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Synaptically-targeted long non-coding RNA SLAMR promotes structural plasticity by increasing translation and CaMKII

Isabel Espadas1, Jenna L Wingfield1, Yoshihisa Nakahata2

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A newly identified long noncoding RNA (lncRNA), SLAMR, is crucial for synaptic plasticity and memory consolidation. Its transport and function in hippocampal neurons impact dendritic complexity and fear memory formation.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Long noncoding RNAs (lncRNAs) are vital for cellular functions.
  • The impact of neuronal activity on lncRNA regulation and memory formation is largely unknown.

Purpose of the Study:

  • To investigate the role of neuronal activity-regulated lncRNAs in synaptic plasticity and memory.
  • To identify and characterize novel lncRNAs involved in learning and memory.

Main Methods:

  • Identification of SLAMR in hippocampal CA1 neurons after fear conditioning.
  • Analysis of SLAMR transport via KIF5C and synaptic recruitment.
  • Investigating loss-of-function and gain-of-function effects on neuronal structure and plasticity.
  • Proteomic analysis of SLAMR interactome and CaMKIIα activity.
  • Behavioral testing in mice for fear memory consolidation and spatial memory.

Main Results:

  • SLAMR is enriched in CA1 neurons post-conditioning and transported along dendrites.
  • SLAMR regulates dendritic complexity, spine plasticity, and translation.
  • SLAMR interacts with CaMKIIα, influencing its activity.
  • Loss of SLAMR function impairs fear memory consolidation in male mice.

Conclusions:

  • SLAMR is a key player in activity-dependent synaptic plasticity.
  • SLAMR is essential for the consolidation of contextual fear memory.
  • This study reveals novel insights into lncRNA function in memory formation.