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R-Ras contributes to LTP and contextual discrimination.

M J Darcy1, S-X Jin1, L A Feig2

  • 1Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, United States.

Neuroscience
|July 22, 2014
PubMed
Summary

Researchers identified R-Ras as a novel regulator of contextual discrimination learning in the hippocampus. This finding is crucial for understanding learning and memory deficits in neurodegenerative diseases like Alzheimer's.

Keywords:
Ras-GRF1hippocampussynaptic plasticity

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Contextual discrimination is a hippocampal-dependent learning form.
  • This learning is impaired in Alzheimer's and Down Syndrome.
  • Ras-GRF1 is known to be important for this learning and memory.

Purpose of the Study:

  • To investigate the role of R-Ras in hippocampal-dependent contextual discrimination.
  • To explore the signaling pathways involved in this learning process.

Main Methods:

  • Utilized virally-delivered microRNAs (miRNAs) to target R-Ras in the CA1 region of the dorsal hippocampus.
  • Assessed contextual discrimination abilities and high-frequency stimulation long-term potentiation (HFS-LTP).
  • Investigated the involvement of p38 Map kinase signaling.

Main Results:

  • Knockdown of R-Ras impaired contextual discrimination.
  • R-Ras knockdown also impaired HFS-LTP induction and p38 Map kinase activation.
  • The role of R-Ras in HFS-LTP for contextual discrimination was independent of Ras-GRF1.

Conclusions:

  • R-Ras is a novel regulator of hippocampal-dependent learning and memory.
  • R-Ras plays a critical role in contextual discrimination, a process affected in neurodegenerative diseases.
  • This study elucidates new signaling pathways relevant to cognitive decline.