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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
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.
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.
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