RSK2 signaling in brain habenula contributes to place aversion learning

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Emmanuel Darcq1, Pascale Koebel, Carolina Del Boca

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université de Strasbourg, 67404 Illkirch, France.

Learning & Memory (Cold Spring Harbor, N.Y.)
|August 20, 2011
PubMed

Insights

Ribosomal S6 Kinase 2 (RSK2) is crucial for cognitive functions, particularly in associating negative stimuli with context. RSK2 signaling in the habenula is essential for this learning process.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Ribosomal S6 Kinase 2 (RSK2) is a serine/threonine kinase involved in the Ras/MAPK pathway.
  • Deficiency in the Rsk2 gene causes Coffin-Lowry Syndrome, which is associated with significant cognitive impairments.

Purpose of the Study:

  • To investigate the role of RSK2 in cognitive processes, specifically in associative learning and emotional processing.
  • To determine the involvement of the habenula in context-dependent aversion learning mediated by RSK2.

Main Methods:

  • Utilized a lithium-induced conditioned place aversion task in mrsk2 knockout mice.
  • Employed virally mediated short hairpin RNA (shRNA) to knockdown RSK2 expression in the habenula.

Main Results:

  • Mice lacking the mrsk2 gene failed to associate an aversive stimulus with a specific context.
  • Knockdown of RSK2 in the habenula using shRNA also abolished contextual conditioning.
  • RSK2 signaling within the habenula was demonstrated to be critical for this form of learning.

Conclusions:

  • RSK2 plays a novel and essential role in higher-order cognitive functions, including associative learning.
  • The habenula is a key brain structure implicated in place aversion learning, modulated by RSK2 signaling.

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