دورية أكاديمية

mTORC1 function in hippocampal parvalbumin interneurons: regulation of firing and long‑term potentiation of intrinsic excitability but not long‑term contextual fear memory and context discrimination ; Mol Brain

التفاصيل البيبلوغرافية
العنوان: mTORC1 function in hippocampal parvalbumin interneurons: regulation of firing and long‑term potentiation of intrinsic excitability but not long‑term contextual fear memory and context discrimination ; Mol Brain
المؤلفون: KHLAIFIA, Abdessattar, HONORE, Eve, ARTINIAN, Julien, LAPLANTE, Isabel, LACAILLE, Jean-Claude
سنة النشر: 2022
مصطلحات موضوعية: 4 Aminobutyric Acid Receptor, Ketamine, Mammalian Target Of Rapamycin Complex 1, Parvalbumin, Regulatory Associated Protein Of Mtor, S6 Kinase, Xylazine, Animal Cell, Animal Experiment, Animal Tissue, Antidromic Stimulation, Article, Controlled Study, Fear, Fear Conditioning Test, Female, Firing Rate, Hippocampal Ca1 Region, Hippocampal Slice, Hippocampus Potential, Homozygosity, Immunofluorescence, Interneuron, Long Term Memory, Long Term Potentiation, Male, Mouse, Mtor Signaling, Nerve Excitability, Nonhuman
الوصف: Hippocampal CA1 parvalbumin-expressing interneurons (PV INs) play a central role in controlling principal cell activity and orchestrating network oscillations. PV INs receive excitatory inputs from CA3 Schaffer collaterals and local CA1 pyramidal cells, and they provide perisomatic inhibition. Schaffer collateral excitatory synapses onto PV INs express Hebbian and anti-Hebbian types of long-term potentiation (LTP), as well as elicit LTP of intrinsic excitability (LTPIE). LTPIE requires the activation of type 5 metabotropic glutamate receptors (mGluR5) and is mediated by downregulation of potassium channels Kv1.1. It is sensitive to rapamycin and thus may involve activation of the mammalian target of rapamycin complex 1 (mTORC1). LTPIE facilitates PV INs recruitment in CA1 and maintains an excitatory-inhibitory balance. Impaired CA1 PV INs activity or LTP affects network oscillations and memory. However, whether LTPIE in PV INs plays a role in hippocampus-dependent memory remains unknown. Here, we used conditional deletion of the obligatory component of mTORC1, the Regulatory-Associated Protein of mTOR (Raptor), to directly manipulate mTORC1 in PV INs. We found that homozygous, but not heterozygous, conditional knock-out of Rptor resulted in a decrease in CA1 PV INs of mTORC1 signaling via its downstream effector S6 phosphorylation assessed by immunofluorescence. In whole-cell recordings from hippocampal slices, repetitive firing of CA1 PV INs was impaired in mice with either homozygous or heterozygous conditional knock-out of Rptor. High frequency stimulation of Schaffer collateral inputs that induce LTPIE in PV INs of control mice failed to do so in mice with either heterozygous or homozygous conditional knock-out of Rptor in PV INs. At the behavioral level, mice with homozygous or heterozygous conditional knock-out of Rptor showed similar long-term contextual fear memory or contextual fear memory discrimination relative to control mice. Thus, mTORC1 activity in CA1 PV INs regulates repetitive firing and LTPIE ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 1756-6606
العلاقة: https://oskar-bordeaux.fr/handle/20.500.12278/170246Test
DOI: 10.1186/s13041-022-00941-8
الإتاحة: https://doi.org/20.500.12278/170246Test
https://doi.org/10.1186/s13041-022-00941-8Test
https://oskar-bordeaux.fr/handle/20.500.12278/170246Test
https://hdl.handle.net/20.500.12278/170246Test
حقوق: Attribution 3.0 United States ; open ; http://creativecommons.org/licenses/by/3.0/usTest/ ; CC BY
رقم الانضمام: edsbas.3E6169E2
قاعدة البيانات: BASE
الوصف
تدمد:17566606
DOI:10.1186/s13041-022-00941-8