Regulation of Hippocampal Memory by mTORC1 in Somatostatin Interneurons
Bibliographic record
Abstract
Translational control of long-term synaptic plasticity via Mechanistic Target Of Rapamycin Complex 1 (mTORC1) is crucial for hippocampal learning and memory. The role of mTORC1 is well characterized in excitatory principal cells but remains largely unaddressed in inhibitory interneurons. Here, we used cell-type-specific conditional knock-out strategies to alter mTORC1 function selectively in somatostatin (SOM) inhibitory interneurons (SOM-INs). We found that, in male mice, upregulation and downregulation of SOM-IN mTORC1 activity bidirectionally regulates contextual fear and spatial memory consolidation. Moreover, contextual fear learning induced a metabotropic glutamate receptor type 1 (mGluR1)-mediated late long-term potentiation (LTP) of excitatory input synapses onto hippocampal SOM-INs that was dependent on mTORC1. Finally, the induction protocol for mTORC1-mediated late-LTP in SOM-INs regulated Schaffer collateral pathway LTP in pyramidal neurons. Therefore, mTORC1 activity in somatostatin interneurons contributes to learning-induced persistent plasticity of their excitatory synaptic inputs and hippocampal memory consolidation, uncovering a role of mTORC1 in inhibitory circuits for memory. SIGNIFICANCE STATEMENT Memory consolidation necessitates synthesis of new proteins. Mechanistic Target Of Rapamycin Complex 1 (mTORC1) signaling is crucial for translational control involved in long-term memory and in late long-term potentiation (LTP). This is well described in principal glutamatergic pyramidal cells but poorly understood in GABAergic inhibitory interneurons. Here, we show that mTORC1 activity in somatostatin interneurons, a major subclass of GABAergic cells, is important to modulate long-term memory strength and precision. Furthermore, mTORC1 was necessary for learning-induced persistent LTP at excitatory inputs of somatostatin interneurons that depends on type I metabotropic glutamatergic receptors in the hippocampus. This effect was consistent with a newly described role of these interneurons in the modulation of LTP at Schaffer collateral synapses onto pyramidal cells.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".