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
ARTINIAN, Julien
Université de Montréal [UdeM]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
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Université de Montréal [UdeM]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
ARTINIAN, Julien
Université de Montréal [UdeM]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
< Réduire
Université de Montréal [UdeM]
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
Langue
EN
Article de revue
Ce document a été publié dans
Molecular Brain. 2022-06-17, vol. 15, n° 1, p. 56
Résumé en anglais
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 ...Lire la suite >
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 but not consolidation of long-term contextual fear memory and context discrimination. Our results indicate that mTORC1 plays cell-specific roles in synaptic plasticity of hippocampal inhibitory interneurons that are differentially involved in hippocampus-dependent learning and memory. © 2022, The Author(s).< Réduire
Mots clés en anglais
4 Aminobutyric Acid Receptor
Ketamine
Mammalian Target Of Rapamycin Complex 1
Parvalbumin
Regulatory Associated Protein Of Mtor
S6 Kinase
Xylazine
Mammalian Target Of Rapamycin Complex 1
Parvalbumin
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
Protein Function
Protein Phosphorylation
Schaffer Collateral Pathway
Whole Cell Patch Clamp
Animal
Hippocampus
Interneuron
Mammal
Metabolism
Physiology
Synapse
Animals
Fear
Hippocampus
Interneurons
Long-Term Potentiation
Mammals
Mechanistic Target Of Rapamycin Complex 1
Mice
Parvalbumins
Synapses
Unités de recherche