| First Author | Artinian J | Year | 2019 |
| Journal | J Neurosci | Volume | 39 |
| Issue | 43 | Pages | 8439-8456 |
| PubMed ID | 31519824 | Mgi Jnum | J:280626 |
| Mgi Id | MGI:6368935 | Doi | 10.1523/JNEUROSCI.0728-19.2019 |
| Citation | Artinian J, et al. (2019) Regulation of Hippocampal Memory by mTORC1 in Somatostatin Interneurons. J Neurosci 39(43):8439-8456 |
| abstractText | 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. |
