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MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice

The proper development and function of neuronal circuits rely on a tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission, and disrupting this balance can cause neurodevelopmental disorders, for example, schizophrenia. MicroRNA-dependent gene regulation in pyramidal...

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Main Authors: Daswani, Reetu Ramesh (Author) , Gilardi, Carlotta (Author) , Soutschek, Michael (Author) , Nanda, Prakruti (Author) , Weiss, Kerstin (Author) , Bicker, Silvia (Author) , Fiore, Roberto (Author) , Dieterich, Christoph (Author) , Germain, Pierre-Luc (Author) , Winterer, Jochen (Author) , Schratt, Gerhard (Author)
Format: Article (Journal)
Language:English
Published: 15 March 2022
In: eLife
Year: 2022, Volume: 11, Pages: 1-24
ISSN:2050-084X
DOI:10.7554/eLife.74056
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.7554/eLife.74056
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Author Notes:Reetu Daswani, Carlotta Gilardi, Michael Soutschek, Prakruti Nanda, Kerstin Weiss, Silvia Bicker, Roberto Fiore, Christoph Dieterich, Pierre-Luc Germain, Jochen Winterer, Gerhard Schratt
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Summary:The proper development and function of neuronal circuits rely on a tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission, and disrupting this balance can cause neurodevelopmental disorders, for example, schizophrenia. MicroRNA-dependent gene regulation in pyramidal neurons is important for excitatory synaptic function and cognition, but its role in inhibitory interneurons is poorly understood. Here, we identify miR138-5p as a regulator of short-term memory and inhibitory synaptic transmission in the mouse hippocampus. Sponge-mediated miR138-5p inactivation specifically in mouse parvalbumin (PV)-expressing interneurons impairs spatial recognition memory and enhances GABAergic synaptic input onto pyramidal neurons. Cellular and behavioral phenotypes associated with miR138-5p inactivation are paralleled by an upregulation of the schizophrenia (SCZ)-associated Erbb4, which we validated as a direct miR138-5p target gene. Our findings suggest that miR138-5p is a critical regulator of PV interneuron function in mice, with implications for cognition and SCZ. More generally, they provide evidence that microRNAs orchestrate neural circuit development by fine-tuning both excitatory and inhibitory synaptic transmission.
Item Description:Version of record published: March 29, 2022 (version 2)
Mit zusätzlichen Informationen: Brief zur Entscheidung und Antwort der Autoren
Gesehen am 23.06.2022
Physical Description:Online Resource
ISSN:2050-084X
DOI:10.7554/eLife.74056

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