Persistent transcription- and translation-dependent long-term potentiation induced by mGluR1 in hippocampal interneurons

mGluR1 在海马中间神经元中诱导的持续转录和翻译依赖性长期增强

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作者:Israeli Ran, Isabel Laplante, Catherine Bourgeois, Julie Pépin, Philippe Lacaille, Mauro Costa-Mattioli, Jerry Pelletier, Nahum Sonenberg, Jean-Claude Lacaille

Abstract

Hippocampal interneurons synchronize the activity of large neuronal ensembles during memory consolidation. Although the latter process is manifested as increases in synaptic efficacy which require new protein synthesis in pyramidal neurons, it is unknown whether such enduring plasticity occurs in interneurons. Here, we uncover a long-term potentiation (LTP) of transmission at individual interneuron excitatory synapses which persists for at least 24 h, after repetitive activation of type-1 metabotropic glutamate receptors [mGluR1-mediated chemical late LTP (cL-LTP(mGluR1))]. cL-LTP(mGluR1) involves presynaptic and postsynaptic expression mechanisms and requires both transcription and translation via phosphoinositide 3-kinase/mammalian target of rapamycin and MAP kinase kinase-extracellular signal-regulated protein kinase signaling pathways. Moreover, cL-LTP(mGluR1) involves translational control at the level of initiation as it is prevented by hippuristanol, an inhibitor of eIF4A, and facilitated in mice lacking the cap-dependent translational repressor, 4E-BP. Our results reveal novel mechanisms of long-term synaptic plasticity that are transcription and translation-dependent in inhibitory interneurons, indicating that persistent synaptic modifications in interneuron circuits may contribute to hippocampal-dependent cognitive processes.

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