Hippocampal Inhibitory Interneuron‐Specific DREADDs Treatment Alters mTORC1‐4E‐BP Signaling and Impairs Memory Formation DOI Creative Commons
Ziying Huang, Niaz Mahmood, Jean‐Claude Lacaille

и другие.

Journal of Neurochemistry, Год журнала: 2025, Номер 169(3)

Опубликована: Март 1, 2025

ABSTRACT Control of protein synthesis via the mechanistic target rapamycin complex 1 (mTORC1) is essential for learning and memory. However, cell‐type‐specific spatiotemporal regulation this pathway during memory formation not well understood. In study, we expressed artificial human muscarinic M3 [hM3D(Gq)] or M4 [hM4D(Gi)] designer receptors exclusively activated by drugs (DREADDs) in hippocampal CA1 excitatory inhibitory neurons adult mice. We studied impact clozapine‐N‐oxide (CNO), a synthetic DREADDs agonist, on mTORC1 long‐term hM3D(Gq) hM4D(Gi) activate inactivate, respectively, signaling interneurons, as indicated phosphorylation its targets, eukaryotic initiation factor 4E‐binding proteins (4E‐BP1/2) ribosomal S6 (S6). Activation either mice immediately after training tasks impaired inhibitory, but neurons. The findings underscore importance activity‐dependent mTORC1–4E‐BP1/2 interneurons formation. image

Язык: Английский

Hippocampal Inhibitory Interneuron‐Specific DREADDs Treatment Alters mTORC1‐4E‐BP Signaling and Impairs Memory Formation DOI Creative Commons
Ziying Huang, Niaz Mahmood, Jean‐Claude Lacaille

и другие.

Journal of Neurochemistry, Год журнала: 2025, Номер 169(3)

Опубликована: Март 1, 2025

ABSTRACT Control of protein synthesis via the mechanistic target rapamycin complex 1 (mTORC1) is essential for learning and memory. However, cell‐type‐specific spatiotemporal regulation this pathway during memory formation not well understood. In study, we expressed artificial human muscarinic M3 [hM3D(Gq)] or M4 [hM4D(Gi)] designer receptors exclusively activated by drugs (DREADDs) in hippocampal CA1 excitatory inhibitory neurons adult mice. We studied impact clozapine‐N‐oxide (CNO), a synthetic DREADDs agonist, on mTORC1 long‐term hM3D(Gq) hM4D(Gi) activate inactivate, respectively, signaling interneurons, as indicated phosphorylation its targets, eukaryotic initiation factor 4E‐binding proteins (4E‐BP1/2) ribosomal S6 (S6). Activation either mice immediately after training tasks impaired inhibitory, but neurons. The findings underscore importance activity‐dependent mTORC1–4E‐BP1/2 interneurons formation. image

Язык: Английский

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