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Blocking mTORC1 activity by rapamycin leads to impairment of spatial memory retrieval but not acquisition in C57BL/6J
Alev Deli1, Katharina Schipany, Margit Rosner
1Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18, 1090 Vienna, Austria.
Abstract:
Although the involvement of the mTOR (mammalian target of rapamycin) system in memory processes has been reported, information on the effect of rapamycin on spatial learning and memory is limited. It was therefore the aim of the study to show the effect of parenteral rapamycin administration to C57BL/6J mice on performance in the multiple T-maze (MTM) and to determine hippocampal mTOR activity. Rapamycin-treated and -untreated/trained/probed mice are the main part of the experiment considering retrieval and acquisition or consolidation of spatial memory. Six hours following euthanasia hippocampi were extirpated and used for evaluation of mTOR activity as represented by hippocampal levels of S6 protein and its phosphorylated active form (phospho S6 protein, S240,244), a read out of mTOR complex 1 activity. Mice given i.p. rapamycin learned the task of the MTM but failed at the probe trial, showing absence of the phosphorylated active form of S6 protein, indicating inhibition of mTOR activity. Herein, impairing effects of rapamycin on retrieval but not on acquisition or consolidation of spatial memory are shown. Deficient memory retrieval was paralleled by inhibition of mTOR complex 1 activity. The current study extends knowledge on rapamycin in memory mechanisms and challenges work on deeper insights into the role of mTOR in different phases of memory formation and retrieval.
Insights
Rapamycin impairs spatial memory retrieval in mice by inhibiting mTOR complex 1 activity, affecting S6 protein phosphorylation without impacting learning or memory consolidation.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- The mammalian target of rapamycin (mTOR) system plays a role in memory processes.
- Limited information exists regarding rapamycin's specific effects on spatial learning and memory.
Purpose of the Study:
- To investigate the impact of parenteral rapamycin administration on spatial memory performance in C57BL/6J mice using the multiple T-maze (MTM).
- To assess the effect of rapamycin on hippocampal mTOR activity, specifically measuring S6 protein and phospho-S6 levels.
Main Methods:
- C57BL/6J mice received intraperitoneal rapamycin injections.
- Spatial memory was evaluated using the multiple T-maze (MTM) for acquisition, consolidation, and retrieval phases.
- Hippocampal mTOR activity was measured by quantifying S6 protein and its phosphorylated active form (phospho S6 protein, S240,244) post-euthanasia.
Main Results:
- Rapamycin-treated mice successfully learned the MTM task but failed during the probe trial.
- Inhibition of mTOR activity was confirmed by the absence of phosphorylated S6 protein in the hippocampi of rapamycin-treated mice.
- Rapamycin impaired spatial memory retrieval but did not affect acquisition or consolidation.
Conclusions:
- Rapamycin administration impairs spatial memory retrieval in mice.
- The observed memory deficits correlate with the inhibition of mTOR complex 1 activity.
- This study highlights the critical role of mTORC1 in memory retrieval and suggests further research into mTOR's function across different memory phases.
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