c-Abl regulates a synaptic plasticity-related transcriptional program involved in memory and learning

Adrián González-Martín, Tomás Moyano, Daniela A Gutiérrez, Franciso J Carvajal, Waldo Cerpa, Jonathan G Hanley, Rodrigo A Gutiérrez, Alejandra R Álvarez

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Memory consolidation requires activation of a gene expression program that allows de novo protein synthesis. But the molecular mechanisms that favour or restrict that program are poorly understood. The kinase c-Abl can modulate gene expression through transcription factors and chromatin modifiers. Here, we show that c-Abl ablation in the brain improves learning acquisition and memory consolidation in mice. Its absence also affects gene expression profiles in the mouse hippocampus. We found that genes involved in synaptic plasticity and actin cytoskeleton dynamics, such as Arp2 and Thorase, are up-regulated at the mRNA and protein levels in trained c-Abl KO mice and by a chemical-LTP stimulus. Trained c-Abl KO mice also show that dendritic spines are larger than in wild-type mice and present at a higher density. These results indicate that c-Abl kinase is an important part of the mechanism that limits or restricts signalling of relevant gene programs involved in morphological and functional spine changes upon neuronal stimulation.

Original languageEnglish
Article number102122
Pages (from-to)102122
JournalProgress in Neurobiology
Early online date18 Jul 2021
DOIs
Publication statusE-pub ahead of print - 18 Jul 2021

Bibliographical note

Funding Information:
This work was supported by FONDECYT grant 1161065 and 1201668 , FONDEF D10E1077 (A.A.) and CONICYT grant 63140177 (A.G.M.) acknowledges support from VRI and CARE UC AFB170005 . 1 1 2 2

Publisher Copyright:
© 2021 Elsevier Ltd

Keywords

  • c-Abl
  • memory and learning
  • transcriptional regulation
  • synaptic plasticity
  • spine morphology
  • hippocampal RNAseq

Fingerprint

Dive into the research topics of 'c-Abl regulates a synaptic plasticity-related transcriptional program involved in memory and learning'. Together they form a unique fingerprint.

Cite this