Loss of 4E-BP converts cerebellar long-term depression to long-term potentiation.

Genetic perturbances in translational regulation result in defects in cerebellar motor learning; however, little is known about the role of translational mechanisms in the regulation of cerebellar plasticity. We show that genetic removal of 4E-BP, a translational suppressor and target of mammalian target of rapamycin complex 1, results in a striking change in cerebellar synaptic plasticity. We find that cerebellar long-term depression (LTD) at parallel fiber-Purkinje cell synapses is converted to long-term potentiation in 4E-BP knockout mice. Biochemical and pharmacological experiments suggest that increased phosphatase activity largely accounts for the defects in LTD. Our results point to a model in which translational regulation through the action of 4E-BP plays a critical role in establishing the appropriate kinase/phosphatase balance required for normal synaptic plasticity in the cerebellum. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Natasha Saviuk, Yumaine Chong, Peng Wang, Sara Bermudez, Zhe Zhao, Arjun A Bhaskaran, Derek Bowie, Nahum Sonenberg, Ellis Cooper, A Pejmun Haghighi. Loss of 4E-BP converts cerebellar long-term depression to long-term potentiation. Cell reports. 2022 Jun 07;39(10):110911

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PMID: 35675781

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